Molecular Genetics and Genomics

, Volume 290, Issue 4, pp 1191–1221 | Cite as

Current review of genetics of human obesity: from molecular mechanisms to an evolutionary perspective

  • David Albuquerque
  • Eric Stice
  • Raquel Rodríguez-López
  • Licíno Manco
  • Clévio Nóbrega
Review

Abstract

It is well-known that obesity is a complex multifactorial and heterogeneous condition with an important genetic component. Recently, major advances in obesity research emerged concerning the molecular mechanisms contributing to the obese condition. This review outlines several studies and data concerning the genetics and other important factors in the susceptibility risk to develop obesity. Based in the genetic etiology three main categories of obesity are considered: monogenic, syndromic, and common obesity. For the monogenic forms of obesity, the gene causing the phenotype is clearly identified, whereas for the common obesity the loci architecture underlying the phenotype is still being characterized. Given that, in this review we focus mainly in this obesity form, reviewing loci found until now by genome-wide association studies related with the susceptibility risk to develop obesity. Moreover, we also detail the obesity-related loci identified in children and in different ethnic groups, trying to highlight the complexity of the genetics underlying the common obese phenotype. Importantly, we also focus in the evolutionary hypotheses that have been proposed trying to explain how natural selection favored the spread of genes that increase the risk for an obese phenotype and how this predisposition to obesity evolved. Other factors are important in the obesity condition, and thus, we also discuss the epigenetic mechanisms involved in the susceptibility and development of obesity. Covering all these topics we expect to provide a complete and recent perspective about the underlying mechanisms involved in the development and origin of obesity. Only with a full understanding of the factors and mechanisms contributing to obesity, it will be possible to provide and allow the development of new therapeutic approaches to this condition.

Keywords

Obesity Genetics of obesity Epigenetics MicroRNAs Evolutionary perspectives Nutrigenomics 

Notes

Acknowledgments

David Albuquerque as a PhD grant (SFRH/BD/68774/2010) from Fundação para a Ciência e a Tecnologia (FCT).

Conflict of interest

All the authors recognize and disclose to have no conflict of interest to declare.

References

  1. Ahmad S, Rukh G, Varga TV, Ali A, Kurbasic A, Shungin D, Ericson U, Koivula RW, Chu AY, Rose LM, Ganna A, Qi Q, Stančáková A, Sandholt CH, Elks CE, Curhan G, Jensen MK, Tamimi RM, Allin KH, Jørgensen T, Brage S, Langenberg C, Aadahl M, Grarup N, Linneberg A, Paré G, InterAct Consortium, DIRECT Consortium, Magnusson PK, Pedersen NL, Boehnke M, Hamsten A, Mohlke KL, Pasquale LT, Pedersen O, Scott RA, Ridker PM, Ingelsson E, Laakso M, Hansen T, Qi L, Wareham NJ, Chasman DI, Hallmans G, Hu FB, Renström F, Orho-Melander M, Franks PW (2013) Gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry. PLoS Genet 9(7):e1003607PubMedCentralPubMedGoogle Scholar
  2. Albuquerque D, Nóbrega C, Manco L (2013a) Association of FTO polymorphisms with obesity and obesity-related outcomes in Portuguese children. PLoS One 8(1):e54370PubMedCentralPubMedGoogle Scholar
  3. Albuquerque D, Nóbrega C, Manco L (2013b) The lactase persistence-13910C>T polymorphism shows indication of association with abdominal obesity among Portuguese children. Acta Paediatr 102(4):e153–e157PubMedGoogle Scholar
  4. Albuquerque D, Nóbrega C, Rodríguez-López R, Manco L (2014) Association study of common polymorphisms in MSRA, TFAP2B, MC4R, NRXN3, PPARGC1A, TMEM18, SEC16B, HOXB5, and OLFM4 genes with obesity-related traits among Portuguese children. J Hum Genet 59:307–313PubMedGoogle Scholar
  5. Almén MS, Jacobsson JA, Moschonis G, Benedict C, Chrousos GP, Fredriksson R, Schiöth HB (2012) Genome wide analysis reveals association of a FTO gene variant with epigenetic changes. Genomics 99(3):132–137PubMedGoogle Scholar
  6. Almon R, Alvarez-Leon EE, Serra-Majem L (2012) Association of the European lactase persistence variant (LCT-13910 C>T polymorphism) with obesity in the Canary Islands. PLoS ONE 7:e43978PubMedCentralPubMedGoogle Scholar
  7. Ambros V (2004) The functions of animal microRNAs. Nature 431:350–355PubMedGoogle Scholar
  8. Andreasen CH, Stender-Petersen KL, Mogensen MS, Torekov SS, Wegner L, Andersen G, Nielsen AL, Albrechtsen A, Borch-Johnsen K, Rasmussen SS, Clausen JO, Sandbaek A, Lauritzen T, Hansen L, Jørgensen T, Pedersen O, Hansen T (2008) Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation. Diabetes 57(1):95–101PubMedGoogle Scholar
  9. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297PubMedGoogle Scholar
  10. Bastien M, Poirier P, Lemieux I, Després JP (2014) Overview of epidemiology and contribution of obesity to cardiovascular disease. Prog Cardiovasc Dis 56(4):369–381PubMedGoogle Scholar
  11. Bates SH, Myers MG (2003) The role of leptin receptor signaling in feeding and neuroendocrine function. Trends Endocrinol Metab 14:447–452PubMedGoogle Scholar
  12. Beckers S, Mertens I, Peeters A, Van Gaal L, Van Hul W (2006) Screening for melanocortin-4 receptor mutations in a cohort of Belgian morbidly obese adults and children. Int J Obes (Lond) 30:221–225Google Scholar
  13. Bell AC, Kremer PJ, Magarey AM, Swinburn BA (2005) Contribution of ‘noncore’ foods and beverages to the energy intake and weight status of Australian children. Eur J Clin Nutr 59:639–645PubMedGoogle Scholar
  14. Belsky DW, Moffitt TE, Sugden K, Williams B, Houts R, McCarthy J, Caspi A (2013) Development and evaluation of a genetic risk score for obesity. Biodemogr Soc Biol 59(1):85–100Google Scholar
  15. Bergmann C (2012) Ciliopathies. Eur J Pediatr 171(9):1285–1300PubMedCentralPubMedGoogle Scholar
  16. Berndt SI, Gustafsson S, Mägi R, Ganna A, Wheeler E, Feitosa MF, Justice AE, Monda KL, Croteau-Chonka DC, Day FR, Esko T, Fall T, Ferreira T, Gentilini D, Jackson AU, Luan J, Randall JC, Vedantam S, Willer CJ, Winkler TW, Wood AR, Workalemahu T, Hu YJ, Lee SH, Liang L, Lin DY, Min JL, Neale BM, Thorleifsson G, Yang J, Albrecht E, Amin N, Bragg-Gresham JL, Cadby G, den Heijer M, Eklund N, Fischer K, Goel A, Hottenga JJ, Huffman JE, Jarick I, Johansson Å, Johnson T, Kanoni S, Kleber ME, König IR, Kristiansson K, Kutalik Z, Lamina C, Lecoeur C, Li G, Mangino M, McArdle WL, Medina-Gomez C, Müller-Nurasyid M, Ngwa JS, Nolte IM, Paternoster L, Pechlivanis S, Perola M, Peters MJ, Preuss M, Rose LM, Shi J, Shungin D, Smith AV, Strawbridge RJ, Surakka I, Teumer A, Trip MD, Tyrer J, Van Vliet-Ostaptchouk JV, Vandenput L, Waite LL, Zhao JH, Absher D, Asselbergs FW, Atalay M, Attwood AP, Balmforth AJ, Basart H, Beilby J, Bonnycastle LL, Brambilla P, Bruinenberg M, Campbell H, Chasman DI, Chines PS, Collins FS, Connell JM, Cookson WO, de Faire U, de Vegt F, Dei M, Dimitriou M, Edkins S, Estrada K, Evans DM, Farrall M, Ferrario MM, Ferrières J, Franke L, Frau F, Gejman PV, Grallert H, Grönberg H, Gudnason V, Hall AS, Hall P, Hartikainen AL, Hayward C, Heard-Costa NL, Heath AC, Hebebrand J, Homuth G, Hu FB, Hunt SE, Hyppönen E, Iribarren C, Jacobs KB, Jansson JO, Jula A, Kähönen M, Kathiresan S, Kee F, Khaw KT, Kivimäki M, Koenig W, Kraja AT, Kumari M, Kuulasmaa K, Kuusisto J, Laitinen JH, Lakka TA, Langenberg C, Launer LJ, Lind L, Lindström J, Liu J, Liuzzi A, Lokki ML, Lorentzon M, Madden PA, Magnusson PK, Manunta P, Marek D, März W, Mateo Leach I, McKnight B, Medland SE, Mihailov E, Milani L, Montgomery GW, Mooser V, Mühleisen TW, Munroe PB, Musk AW, Narisu N, Navis G, Nicholson G, Nohr EA, Ong KK, Oostra BA, Palmer CN, Palotie A, Peden JF, Pedersen N, Peters A, Polasek O, Pouta A, Pramstaller PP, Prokopenko I, Pütter C, Radhakrishnan A, Raitakari O, Rendon A, Rivadeneira F, Rudan I, Saaristo TE, Sambrook JG, Sanders AR, Sanna S, Saramies J, Schipf S, Schreiber S, Schunkert H, Shin SY, Signorini S, Sinisalo J, Skrobek B, Soranzo N, Stančáková A, Stark K, Stephens JC, Stirrups K, Stolk RP, Stumvoll M, Swift AJ, Theodoraki EV, Thorand B, Tregouet DA, Tremoli E, Van der Klauw MM, van Meurs JB, Vermeulen SH, Viikari J, Virtamo J, Vitart V, Waeber G, Wang Z, Widén E, Wild SH, Willemsen G, Winkelmann BR, Witteman JC, Wolffenbuttel BH, Wong A, Wright AF, Zillikens MC, Amouyel P, Boehm BO, Boerwinkle E, Boomsma DI, Caulfield MJ, Chanock SJ, Cupples LA, Cusi D, Dedoussis GV, Erdmann J, Eriksson JG, Franks PW, Froguel P, Gieger C, Gyllensten U, Hamsten A, Harris TB, Hengstenberg C, Hicks AA, Hingorani A, Hinney A, Hofman A, Hovingh KG, Hveem K, Illig T, Jarvelin MR, Jöckel KH, Keinanen-Kiukaanniemi SM, Kiemeney LA, Kuh D, Laakso M, Lehtimäki T, Levinson DF, Martin NG, Metspalu A, Morris AD, Nieminen MS, Njølstad I, Ohlsson C, Oldehinkel AJ, Ouwehand WH, Palmer LJ, Penninx B, Power C, Province MA, Psaty BM, Qi L, Rauramaa R, Ridker PM, Ripatti S, Salomaa V, Samani NJ, Snieder H, Sørensen TI, Spector TD, Stefansson K, Tönjes A, Tuomilehto J, Uitterlinden AG, Uusitupa M, van der Harst P, Vollenweider P, Wallaschofski H, Wareham NJ, Watkins H, Wichmann HE, Wilson JF, Abecasis GR, Assimes TL, Barroso I, Boehnke M, Borecki IB, Deloukas P, Fox CS, Frayling T, Groop LC, Haritunian T, Heid IM, Hunter D, Kaplan RC, Karpe F, Moffatt MF, Mohlke KL, O’Connell JR, Pawitan Y, Schadt EE, Schlessinger D, Steinthorsdottir V, Strachan DP, Thorsteinsdottir U, van Duijn CM, Visscher PM, Di Blasio AM, Hirschhorn JN, Lindgren CM, Morris AP, Meyre D, Scherag A, McCarthy MI, Speliotes EK, North KE, Loos RJ, Ingelsson E (2013) Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture. Nat Genet 45(5):501–512PubMedCentralPubMedGoogle Scholar
  17. Bersaglieri T, Sabeti PC, Patterson N, Vanderploeg T, Schaffner SF, Drake JA, Rhodes M, Reich DE, Hirschhorn JN (2004) Genetic signatures of strong recent positive selection at the lactase gene. Am J Hum Genet 74(6):1111–1120PubMedCentralPubMedGoogle Scholar
  18. Bird A (2002) DNA methylation patterns and epigenetic memory. Genes Dev 16(1):6–21PubMedGoogle Scholar
  19. Blüher M (2014) Mechanisms in endocrinology: are metabolically healthy obese individuals really healthy? Eur J Endocrinol 171(6):R209–R219PubMedGoogle Scholar
  20. Blüher M, Mantzoros CS (2015) From leptin to other adipokines in health and disease: facts and expectations at the beginning of the 21st century. Metabolism 64(1):131–145PubMedGoogle Scholar
  21. Bonnefond A, Philippe J, Durand E, Muller J, Saeed S, Arslan M, Martínez R, De Graeve F, Dhennin V, Rabearivelo I, Polak M, Cavé H, Castaño L, Vaxillaire M, Mandel JL, Sand O, Froguel P (2014) Highly sensitive diagnosis of 43 monogenic forms of diabetes or obesity through one-step PCR-based enrichment in combination with next-generation sequencing. Diabetes Care 37(2):460–467PubMedGoogle Scholar
  22. Bradfield JP, Taal HR, Timpson NJ, Scherag A, Lecoeur C, Warrington NM, Hypponen E, Holst C, Valcarcel B, Thiering E, Salem RM, Schumacher FR, Cousminer DL, Sleiman PM, Zhao J, Berkowitz RI, Vimaleswaran KS, Jarick I, Pennell CE, Evans DM, St Pourcain B, Berry DJ, Mook-Kanamori DO, Hofman A, Rivadeneira F, Uitterlinden AG, van Duijn CM, van der Valk RJ, de Jongste JC, Postma DS, Boomsma DI, Gauderman WJ, Hassanein MT, Lindgren CM, Mägi R, Boreham CA, Neville CE, Moreno LA, Elliott P, Pouta A, Hartikainen AL, Li M, Raitakari O, Lehtimäki T, Eriksson JG, Palotie A, Dallongeville J, Das S, Deloukas P, McMahon G, Ring SM, Kemp JP, Buxton JL, Blakemore AI, Bustamante M, Guxens M, Hirschhorn JN, Gillman MW, Kreiner-Møller E, Bisgaard H, Gilliland FD, Heinrich J, Wheeler E, Barroso I, O’Rahilly S, Meirhaeghe A, Sørensen TI, Power C, Palmer LJ, Hinney A, Widen E, Farooqi IS, McCarthy MI, Froguel P, Meyre D, Hebebrand J, Jarvelin MR, Jaddoe VW, Smith GD, Hakonarson H, Grant SF, Early Growth Genetics Consortium (2012) A genome-wide association meta-analysis identifies new childhood obesity loci. Nat Genet 44:526–531PubMedCentralPubMedGoogle Scholar
  23. Brunaud L, Alberto JM, Ayav A, Gérard P, Namour F, Antunes L, Braun M, Bronowicki JP, Bresler L, Guéant JL (2003) Vitamin B12 is a strong determinant of low methionine synthase activity and DNA hypomethylation in gastrectomized rats. Digestion 68:133–140PubMedGoogle Scholar
  24. Cai G, Cole SA, Butte N, Bacino C, Diego V, Tan K, Göring HH, O’Rahilly S, Farooqi IS, Comuzzie AG (2006) A quantitative trait locus on chromosome 18q for physical activity and dietary intake in Hispanic children. Obesity (Silver Spring) 14:1596–1604Google Scholar
  25. Campión F, Milagro F, Martínez J (2009) Etiology and pathophysiology: individuality and epigenetics in obesity. Obes Rev 10:383–392PubMedGoogle Scholar
  26. Cannon B, Nedergaard J (2004) Brown adipose tissue: function and physiological significance. Physiol Rev 84:277–359PubMedGoogle Scholar
  27. Cascorbi I, Bruhn O, Werk AN (2013) Challenges in pharmacogenetics. Eur J Clin Pharmacol 69(Suppl 1):S17–S23Google Scholar
  28. Chambers JC, Elliott P, Zabaneh D, Zhang W, Li Y, Froguel P, Balding D, Scott J, Kooner JS (2008) Common genetic variation near MC4R is associated with waist circumference and insulin resistance. Nat Genet 40:716–718PubMedGoogle Scholar
  29. Chang YC, Liu PH, Lee WJ, Chang TJ, Jiang YD, Li HY, Kuo SS, Lee KC, Chuang LM (2008) Common variation in the fat mass and obesity-associated (FTO) gene confers risk of obesity and modulates BMI in the Chinese population. Diabetes 57:2245–2252PubMedCentralPubMedGoogle Scholar
  30. Chen J, He X, Huang J (2014) Diet effects in gut microbiome and obesity. J Food Sci 79(4):R442–R451PubMedGoogle Scholar
  31. Choi SW, Friso S, Ghandour H, Bagley PJ, Selhub J, Mason JB (2004) Vitamin B-12 deficiency induces anomalies of base substitution and methylation in the DNA of rat colonic epithelium. J Nutr 134:750–755PubMedGoogle Scholar
  32. Church C, Lee S, Bagg EA, McTaggart JS, Deacon R, Gerken T, Lee A, Moir L, Mecinović J, Quwailid MM, Schofield CJ, Ashcroft FM, Cox RD (2009) A mouse model for the metabolic effects of the human fat mass and obesity associated FTO gene. PLoS Genet 5:e1000599PubMedCentralPubMedGoogle Scholar
  33. Church C, Moir L, McMurray F, Girard C, Banks GT, Teboul L, Wells S, Brüning JC, Nolan PM, Ashcroft FM, Cox RD (2010) Overexpression of Fto leads to increased food intake and results in obesity. Nat Genet 42:1086–1092PubMedCentralPubMedGoogle Scholar
  34. Clément K, Ferré P (2003) Genetics and the pathophysiology of obesity. Pediatr Res 53:721–725PubMedGoogle Scholar
  35. Corella D, Arregui M, Coltell O, Portolés O, Guillem-Sáiz P, Carrasco P, Sorlí JV, Ortega-Azorín C, González JI, Ordovás JM (2011) Association of the LCT-13910C > T polymorphism with obesity and its modulation by dairy products in a Mediterranean population. Obesity (Silver Spring) 19:1707–1714Google Scholar
  36. Cosentino G, Conrad AO, Uwaifo GI (2013) Phentermine and topiramate for the management of obesity: a review. Drug Des Devel Ther 7:267–278PubMedCentralPubMedGoogle Scholar
  37. Costello JF, Plass C (2001) Methylation matters. J Med Genet 38:285–303PubMedCentralPubMedGoogle Scholar
  38. Danielzik S, Langnäse K, Mast M, Spethmann C, Müller MJ (2002) Impact of parental BMI on the manifestation of overweight 5–7 year old children. Eur J Nutr 41(3):132–138PubMedGoogle Scholar
  39. de Luis DA, Pacheco D, Aller R, Izaola O (2014) Role of the rs6923761 gene variant in glucagon-like peptide 1 receptor gene on cardiovascular risk factors and weight loss after Biliopancreatic diversion surgery. Ann Nutr Metab 65(4):259–263PubMedGoogle Scholar
  40. Deliard S, Panossian S, Mentch FD, Kim CE, Hou C, Frackelton EC, Bradfield JP, Glessner JT, Zhang H, Wang K, Sleiman PM, Chiavacci RM, Berkowitz RI, Hakonarson H, Zhao J, Grant SF (2013) The missense variation landscape of FTO, MC4R, and TMEM18 in obese children of African ancestry. Obesity (Silver Spring) 21(1):159–163Google Scholar
  41. Dina C, Meyre D, Gallina S, Durand E, Körner A, Jacobson P, Carlsson LM, Kiess W, Vatin V, Lecoeur C, Delplanque J, Vaillant E, Pattou F, Ruiz J, Weill J, Levy-Marchal C, Horber F, Potoczna N, Hercberg S, Le Stunff C, Bougnères P, Kovacs P, Marre M, Balkau B, Cauchi S, Chèvre JC, Froguel P (2007) Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet 39(6):724–726PubMedGoogle Scholar
  42. Dlouha D, Pitha J, Lanska V, Hubacek JA (2012) Association between FTO 1st intron tagging variant and telomere length in middle aged females. 3PMFs study. Clin Chim Acta 413(15–16):1222–1225PubMedGoogle Scholar
  43. Dubern B, Clément K (2012) Leptin and leptin receptor-related monogenic obesity. Biochimie 94:2111–2115PubMedGoogle Scholar
  44. Elrazek AE, Elbanna AE, Bilasy SE (2014) Medical management of patients after bariatric surgery: principles and guidelines. World J Gastrointest Surg 6(11):220–228PubMedCentralPubMedGoogle Scholar
  45. Enattah NS, Sahi T, Savilahti E, Terwilliger JD, Peltonen L, Jãverlã I (2002) Identification of a variant associated with adult-type hypolactasia. Nat Genet 30:233–237PubMedGoogle Scholar
  46. Fang H, Li Y, Du S, Hu X, Zhang Q, Liu A, Ma G (2010) Variant rs9939609 in the FTO gene is associated with body mass index among Chinese children. BMC Med Genet 11:e136Google Scholar
  47. Farooqi S, O’Rahilly S (2005) Monogenic obesity in humans. Annu Rev Med 56:443–458PubMedGoogle Scholar
  48. Farooqi IS, Keogh JM, Yeo GS, Lank EJ, Cheetham T, O’Rahilly S (2003) Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med 348:1085–1095PubMedGoogle Scholar
  49. Fawcett KA, Barroso I (2010) The genetics of obesity: FTO leads the way. Trends Genet 26(6):266–274PubMedCentralPubMedGoogle Scholar
  50. Feinleib M, Garrison RJ, Fabsitz R, Christian JC, Hrubec Z, Borhani NO, Kannel WB, Rosenman R, Schwartz JT, Wagner JO (1977) The NHLBI twin study of cardiovascular disease risk factors: methodology and summary of results. Am J Epidemiol 106(4):284–285PubMedGoogle Scholar
  51. Feldmann HM, Golozoubova V, Cannon B, Nedergaard J (2009) UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at hermoneutrality. Cell Metab 9:203–209PubMedGoogle Scholar
  52. Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek CJ, Singh GM, Gutierrez HR, Lu Y, Bahalim AN, Farzadfar F, Riley LM, Ezzati M (2011) National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet 377(9765):557–567PubMedCentralPubMedGoogle Scholar
  53. Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T, Brüning JC, Rüther U (2009) Inactivation of the Fto gene protects from obesity. Nature 458:894–898PubMedGoogle Scholar
  54. Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JR, Elliott KS, Lango H, Rayner NW, Shields B, Harries LW, Barrett JC, Ellard S, Groves CJ, Knight B, Patch AM, Ness AR, Ebrahim S, Lawlor DA, Ring SM, Ben-Shlomo Y, Jarvelin MR, Sovio U, Bennett AJ, Melzer D, Ferrucci L, Loos RJ, Barroso I, Wareham NJ, Karpe F, Owen KR, Cardon LR, Walker M, Hitman GA, Palmer CN, Doney AS, Morris AD, Smith GD, Hattersley AT, McCarthy MI (2007) A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316(5826):889–894PubMedCentralPubMedGoogle Scholar
  55. Gantz I, Miwa H, Konda Y, Shimoto Y, Tashiro T, Watson SJ, DelValle J, Yamada T (1993) Molecular cloning, expression, and gene localization of a fourth melanocortin receptor. J Biol Chem 268:15174–15179PubMedGoogle Scholar
  56. Gemma C, Sookoian S, Alvariñas J, García SI, Quintana L, Kanevsky D, González CD, Pirola CJ (2009) Maternal pregestational BMI is associated with methylation of the PPARGC1A promoter in newborns. Obesity (Silver Spring) 17:1032–1039Google Scholar
  57. Gerken T, Girard CA, Tung YC, Webby CJ, Saudek V, Hewitson KS, Yeo GS, McDonough MA, Cunliffe S, McNeill LA, Galvanovskis J, Rorsman P, Robins P, Prieur X, Coll AP, Ma M, Jovanovic Z, Farooqi IS, Sedgwick B, Barroso I, Lindahl T, Ponting CP, Ashcroft FM, O’Rahilly S, Schofield CJ (2007) The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 318:1469–1472PubMedCentralPubMedGoogle Scholar
  58. Godfrey KM, Sheppard A, Gluckman PD, Lillycrop KA, Burdge GC, McLean C, Rodford J, Slater-Jefferies JL, Garratt E, Crozier SR, Emerald BS, Gale CR, Inskip HM, Cooper C, Hanson MA (2011) Epigenetic gene promoter methylation at birth is associated with child’s later adiposity. Diabetes 60:1528–1534PubMedCentralPubMedGoogle Scholar
  59. Goel K, Lopez-Jimenez F, De Schutter A, Coutinho T, Lavie CJ (2014) Obesity paradox in different populations: evidence and controversies. Future Cardiol 10(1):81–91PubMedGoogle Scholar
  60. González JR, González-Carpio M, Hernández-Sáez R, Serrano Vargas V, Torres Hidalgo G, Rubio-Rodrigo M, García-Nogales A, Núñez Estévez M, Luengo Pérez LM, Rodríguez-López R (2012) FTO risk haplotype among early onset and severe obesity cases in a population of western Spain. Obesity (Silver Spring) 20(4):909–915Google Scholar
  61. González JR, Estévez MN, Giralt PS, Cáceres A, Pérez LM, González-Carpio M, Ballester F, Sunyer J, Rodríguez-López R (2013) Genetic risk profiles for a childhood with severely overweight. Pediatr Obes. doi: 10.1111/j.2047-6310.2013.00166.x. [Epub ahead of print]
  62. González-Jiménez E, Aguilar Cordero MJ, Padilla López CA, García García I (2012) Monogenic human obesity: role of the leptin-melanocortin system in the regulation of food intake and body weight in humans. An Sist Sanit Navar 35(2):285–293PubMedGoogle Scholar
  63. Goyal A, Nimmakayala KR, Zonszein J (2014) Is there a paradox in obesity? Cardiol Rev 22(4):163–170PubMedCentralPubMedGoogle Scholar
  64. Grant SF, Li M, Bradfield JP, Kim CE, Annaiah K, Santa E, Glessner JT, Casalunovo T, Frackelton EC, Otieno FG, Shaner JL, Smith RM, Imielinski M, Eckert AW, Chiavacci RM, Berkowitz RI, Hakonarson H (2008) Association analysis of the FTO gene with obesity in children of Caucasian and African ancestry reveals a common tagging SNP. PLoS ONE 3:e1746PubMedCentralPubMedGoogle Scholar
  65. Hallman DM, Friedel VC, Eissa MA, Boerwinkle E, Huber JC Jr, Harrist RB, Srinivasan SR, Chen W, Dai S, Labarthe DR, Berenson GS (2012) The association of variants in the FTO gene with longitudinal body mass index profiles in non-Hispanic white children and adolescents. Int J Obes (Lond). 36(1):61–68PubMedCentralGoogle Scholar
  66. Han Z, Niu T, Chang J, Lei X, Zhao M, Wang Q, Cheng W, Wang J, Feng Y, Chai J (2010) Crystal structure of the FTO protein reveals basis for its substrate specificity. Nature 464:1205–1209PubMedGoogle Scholar
  67. Harrold JA, Williams G (2006) Melanocortin-4 receptors, beta-MSH and leptin: key elements in the satiety pathway. Peptides 27:365–371PubMedGoogle Scholar
  68. Haslam DW, James WP (2005) Obesity. Lancet 366:1197–1209PubMedGoogle Scholar
  69. Hassanein MT, Lyon HN, Nguyen TT, Akylbekova EL, Waters K, Lettre G, Tayo B, Forrester T, Sarpong DF, Stram DO, Butler JL, Wilks R, Liu J, Le Marchand L, Kolonel LN, Zhu X, Henderson B, Cooper R, McKenzie C, Taylor HA Jr, Haiman CA, Hirschhorn JN (2010) Fine mapping of the association with obesity at the FTO locus in African derived populations. Hum Mol Genet 19:2907–2916PubMedCentralPubMedGoogle Scholar
  70. Hatoum IJ, Greenawalt DM, Cotsapas C, Reitman ML, Daly MJ, Kaplan LM (2011) Heritability of the weight loss response to gastric bypass surgery. J Clin Endocrinol Metab 96:E1630–E1633PubMedCentralPubMedGoogle Scholar
  71. Hatoum IJ, Greenawalt DM, Cotsapas C, Daly MJ, Reitman ML, Kaplan LM (2013) Weight loss after gastric bypass is associated with a variant at 15q26.1. Am J Hum Genet 92(5):827–834PubMedCentralPubMedGoogle Scholar
  72. Heard-Costa NL, Zillikens MC, Monda KL, Johansson A, Harris TB, Fu M, Haritunians T, Feitosa MF, Aspelund T, Eiriksdottir G, Garcia M, Launer LJ, Smith AV, Mitchell BD, McArdle PF, Shuldiner AR, Bielinski SJ, Boerwinkle E, Brancati F, Demerath EW, Pankow JS, Arnold AM, Chen YD, Glazer NL, McKnight B, Psaty BM, Rotter JI, Amin N, Campbell H, Gyllensten U, Pattaro C, Pramstaller PP, Rudan I, Struchalin M, Vitart V, Gao X, Kraja A, Province MA, Zhang Q, Atwood LD, Dupuis J, Hirschhorn JN, Jaquish CE, O’Donnell CJ, Vasan RS, White CC, Aulchenko YS, Estrada K, Hofman A, Rivadeneira F, Uitterlinden AG, Witteman JC, Oostra BA, Kaplan RC, Gudnason V, O’Connell JR, Borecki IB, van Duijn CM, Cupples LA, Fox CS, North KE (2009) NRXN3 is a novel locus for waist circumference: a genome-wide association study from the CHARGE Consortium. PLoS Genet 5:e1000539PubMedCentralPubMedGoogle Scholar
  73. Heid IM, Jackson AU, Randall JC, Winkler TW, Qi L, Steinthorsdottir V, Thorleifsson G, Zillikens MC, Speliotes EK, Mägi R, Workalemahu T, White CC, Bouatia-Naji N, Harris TB, Berndt SI, Ingelsson E, Willer CJ, Weedon MN, Luan J, Vedantam S, Esko T, Kilpeläinen TO, Kutalik Z, Li S, Monda KL, Dixon AL, Holmes CC, Kaplan LM, Liang L, Min JL, Moffatt MF, Molony C, Nicholson G, Schadt EE, Zondervan KT, Feitosa MF, Ferreira T, Lango Allen H, Weyant RJ, Wheeler E, Wood AR, MAGIC, Estrada K, Goddard ME, Lettre G, Mangino M, Nyholt DR, Purcell S, Smith AV, Visscher PM, Yang J, McCarroll SA, Nemesh J, Voight BF, Absher D, Amin N, Aspelund T, Coin L, Glazer NL, Hayward C, Heard-Costa NL, Hottenga JJ, Johansson A, Johnson T, Kaakinen M, Kapur K, Ketkar S, Knowles JW, Kraft P, Kraja AT, Lamina C, Leitzmann MF, McKnight B, Morris AP, Ong KK, Perry JR, Peters MJ, Polasek O, Prokopenko I, Rayner NW, Ripatti S, Rivadeneira F, Robertson NR, Sanna S, Sovio U, Surakka I, Teumer A, van Wingerden S, Vitart V, Zhao JH, Cavalcanti-Proença C, Chines PS, Fisher E, Kulzer JR, Lecoeur C, Narisu N, Sandholt C, Scott LJ, Silander K, Stark K, Tammesoo ML, Teslovich TM, Timpson NJ, Watanabe RM, Welch R, Chasman DI, Cooper MN, Jansson JO, Kettunen J, Lawrence RW, Pellikka N, Perola M, Vandenput L, Alavere H, Almgren P, Atwood LD, Bennett AJ, Biffar R, Bonnycastle LL, Bornstein SR, Buchanan TA, Campbell H, Day IN, Dei M, Dörr M, Elliott P, Erdos MR, Eriksson JG, Freimer NB, Fu M, Gaget S, Geus EJ, Gjesing AP, Grallert H, Grässler J, Groves CJ, Guiducci C, Hartikainen AL, Hassanali N, Havulinna AS, Herzig KH, Hicks AA, Hui J, Igl W, Jousilahti P, Jula A, Kajantie E, Kinnunen L, Kolcic I, Koskinen S, Kovacs P, Kroemer HK, Krzelj V, Kuusisto J, Kvaloy K, Laitinen J, Lantieri O, Lathrop GM, Lokki ML, Luben RN, Ludwig B, McArdle WL, McCarthy A, Morken MA, Nelis M, Neville MJ, Paré G, Parker AN, Peden JF, Pichler I, Pietiläinen KH, Platou CG, Pouta A, Ridderstråle M, Samani NJ, Saramies J, Sinisalo J, Smit JH, Strawbridge RJ, Stringham HM, Swift AJ, Teder-Laving M, Thomson B, Usala G, van Meurs JB, van Ommen GJ, Vatin V, Volpato CB, Wallaschofski H, Walters GB, Widen E, Wild SH, Willemsen G, Witte DR, Zgaga L, Zitting P, Beilby JP, James AL, Kähönen M, Lehtimäki T, Nieminen MS, Ohlsson C, Palmer LJ, Raitakari O, Ridker PM, Stumvoll M, Tönjes A, Viikari J, Balkau B, Ben-Shlomo Y, Bergman RN, Boeing H, Smith GD, Ebrahim S, Froguel P, Hansen T, Hengstenberg C, Hveem K, Isomaa B, Jørgensen T, Karpe F, Khaw KT, Laakso M, Lawlor DA, Marre M, Meitinger T, Metspalu A, Midthjell K, Pedersen O, Salomaa V, Schwarz PE, Tuomi T, Tuomilehto J, Valle TT, Wareham NJ, Arnold AM, Beckmann JS, Bergmann S, Boerwinkle E, Boomsma DI, Caulfield MJ, Collins FS, Eiriksdottir G, Gudnason V, Gyllensten U, Hamsten A, Hattersley AT, Hofman A, Hu FB, Illig T, Iribarren C, Jarvelin MR, Kao WH, Kaprio J, Launer LJ, Munroe PB, Oostra B, Penninx BW, Pramstaller PP, Psaty BM, Quertermous T, Rissanen A, Rudan I, Shuldiner AR, Soranzo N, Spector TD, Syvanen AC, Uda M, Uitterlinden A, Völzke H, Vollenweider P, Wilson JF, Witteman JC, Wright AF, Abecasis GR, Boehnke M, Borecki IB, Deloukas P, Frayling TM, Groop LC, Haritunians T, Hunter DJ, Kaplan RC, North KE, O’Connell JR, Peltonen L, Schlessinger D, Strachan DP, Hirschhorn JN, Assimes TL, Wichmann HE, Thorsteinsdottir U, van Duijn CM, Stefansson K, Cupples LA, Loos RJ, Barroso I, McCarthy MI, Fox CS, Mohlke KL, Lindgren CM (2010) Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Nat Genet 42(11):949–960PubMedCentralPubMedGoogle Scholar
  74. Heijmans BT, Tobi EW, Stein AD, Putter H, Blauw GJ, Susser ES, Slagboom PE, Lumey LH (2008) Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci 105(44):17046–17049PubMedCentralPubMedGoogle Scholar
  75. Heneghan HM, Miller N, McAnena OJ, O’Brien T, Kerin MJ (2011) Differential miRNA expression in omental adipose tissue and in the circulation of obese patients identifies novel metabolic biomarkers. J Clin Endocrinol Metab 96:e846–e850PubMedGoogle Scholar
  76. Hennig BJ, Fulford AJ, Sirugo G, Rayco-Solon P, Hattersley AT, Frayling TM, Prentice AM (2009) FTO gene variation and measures of body mass in an African population. BMC Med Genet 10:21PubMedCentralPubMedGoogle Scholar
  77. Herbert A, Gerry NP, McQueen MB, Heid IM, Pfeufer A, Illig T, Wichmann HE, Meitinger T, Hunter D, Hu FB, Colditz G, Hinney A, Hebebrand J, Koberwitz K, Zhu X, Cooper R, Ardlie K, Lyon H, Hirschhorn JN, Laird NM, Lenburg ME, Lange C, Christman MF (2006) A common genetic variant is associated with adult and childhood obesity. Science 312:279–283PubMedGoogle Scholar
  78. Herring MP, Sailors MH, Bray MS (2014) Genetic factors in exercise adoption, adherence and obesity. Obes Rev 15(1):29–39PubMedGoogle Scholar
  79. Hinney A, Vogel CI, Hebebrand J (2010) From monogenic to polygenic obesity: recent advances. Eur Child Adolesc Psychiatry 19(3):297–310PubMedCentralPubMedGoogle Scholar
  80. Hinney A, Volckmar AL, Knoll N (2013) Melanocortin-4 receptor in energy homeostasis and obesity pathogenesis. Prog Mol Biol Transl Sci 114:147–191PubMedGoogle Scholar
  81. Horne BD, Anderson JL, Carlquist JF, Muhlestein JB, Renlund DG, Bair TL, Pearson RR, Camp NJ (2005) Generating genetic risk scores from intermediate phenotypes for use in association studies of clinically significant endpoints. Ann Hum Genet 69(Pt 2):176–186PubMedGoogle Scholar
  82. Hotta K, Nakata Y, Matsuo T, Kamohara S, Kotani K, Komatsu R, Itoh N, Mineo I, Wada J, Masuzaki H, Yoneda M, Nakajima A, Miyazaki S, Tokunaga K, Kawamoto M, Funahashi T, Hamaguchi K, Yamada K, Hanafusa T, Oikawa S, Yoshimatsu H, Nakao K, Sakata T, Matsuzawa Y, Tanaka K, Kamatani N, Nakamura Y (2008) Variations in the FTO gene are associated with severe obesity in the Japanese. J Hum Genet 53(6):546–553PubMedCentralPubMedGoogle Scholar
  83. Huszar D, Lynch CA, Fairchild-Huntress V, Dunmore JH, Fang Q, Berkemeier LR, Gu W, Kesterson RA, Boston BA, Cone RD, Smith FJ, Campfield LA, Burn P, Lee F (1997) Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88:131–141PubMedGoogle Scholar
  84. Ichihara S, Yamada Y (2008) Genetic factors for human obesity. Cell Mol Life Sci 65(7–8):1086–1098PubMedGoogle Scholar
  85. Jacobsson J, Schiöth H, Fredriksson R (2012) The impact of intronic single nucleotide polymorphisms and ethnic diversity for studies on the obesity gene FTO. Obes Rev 13(12):1096–1109PubMedGoogle Scholar
  86. Jia JJ, Tian YB, Cao ZH, Tao LL, Zhang X, Gao SZ, Ge CR, Lin QY, Jois M (2010) The polymorphisms of UCP1 genes associated with fat metabolism, obesity and diabetes. Mol Biol Rep 37:1513–1522PubMedGoogle Scholar
  87. Jia G, Fu Y, Zhao X, Dai Q, Zheng G, Yang Y, Yi C, Lindahl T, Pan T, Yang YG, He C (2011) N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat Chem Biol 7:885–887PubMedCentralPubMedGoogle Scholar
  88. Kajimoto K, Naraba H, Iwai N (2006) MicroRNA and 3T3-L1 pre-adipocyte differentiation. RNA 12:1626–1632PubMedCentralPubMedGoogle Scholar
  89. Karolina DS, Tavintharan S, Armugam A, Sepramaniam S, Pek SLT, Wong MTK, Lim SC, Sum CF, Jeyaseelan K (2012) Circulating miRNA profiles in patients with metabolic syndrome. J Clin Endocrinol Metab 97:e2271–e2276PubMedGoogle Scholar
  90. Keller P, Gburcik V, Petrovic N, Gallagher IJ, Nedergaard J, Cannon B, Timmons JA (2011) Gene-chip studies of adipogenesis-regulated microRNAs in mouse primary adipocytes and human obesity. BMC Endocr Disord 11:7PubMedCentralPubMedGoogle Scholar
  91. Kettunen J, Silander K, Saarela O, Amin N, Müller M, Timpson N, Surakka I, Ripatti S, Laitinen J, Hartikainen AL, Pouta A, Lahermo P, Anttila V, Männistö S, Jula A, Virtamo J, Salomaa V, Lehtimäki T, Raitakari O, Gieger C, Wichmann EH, Van Duijn CM, Smith GD, McCarthy MI, Järvelin MR, Perola M, Peltonen L (2010) European lactase persistence genotype shows evidence of association with increase in body mass index. Hum Mol Genet 19:1129–1136PubMedCentralPubMedGoogle Scholar
  92. Khosla S, Dean W, Brown D, Reik W, Feil R (2001) Culture of preimplantation mouse embryos affects fetal development and the expression of imprinted genes. Biol Reprod 64:918–926PubMedGoogle Scholar
  93. Kilpeläinen TO, Qi L, Brage S, Sharp SJ, Sonestedt E, Demerath E, Ahmad T, Mora S, Kaakinen M, Sandholt CH, Holzapfel C, Autenrieth CS, Hyppönen E, Cauchi S, He M, Kutalik Z, Kumari M, Stančáková A, Meidtner K, Balkau B, Tan JT, Mangino M, Timpson NJ, Song Y, Zillikens MC, Jablonski KA, Garcia ME, Johansson S, Bragg-Gresham JL, Wu Y, van Vliet-Ostaptchouk JV, Onland-Moret NC, Zimmermann E, Rivera NV, Tanaka T, Stringham HM, Silbernagel G, Kanoni S, Feitosa MF, Snitker S, Ruiz JR, Metter J, Larrad MT, Atalay M, Hakanen M, Amin N, Cavalcanti-Proença C, Grøntved A, Hallmans G, Jansson JO, Kuusisto J, Kähönen M, Lutsey PL, Nolan JJ, Palla L, Pedersen O, Pérusse L, Renström F, Scott RA, Shungin D, Sovio U, Tammelin TH, Rönnemaa T, Lakka TA, Uusitupa M, Rios MS, Ferrucci L, Bouchard C, Meirhaeghe A, Fu M, Walker M, Borecki IB, Dedoussis GV, Fritsche A, Ohlsson C, Boehnke M, Bandinelli S, van Duijn CM, Ebrahim S, Lawlor DA, Gudnason V, Harris TB, Sørensen TI, Mohlke KL, Hofman A, Uitterlinden AG, Tuomilehto J, Lehtimäki T, Raitakari O, Isomaa B, Njølstad PR, Florez JC, Liu S, Ness A, Spector TD, Tai ES, Froguel P, Boeing H, Laakso M, Marmot M, Bergmann S, Power C, Khaw KT, Chasman D, Ridker P, Hansen T, Monda KL, Illig T, Järvelin MR, Wareham NJ, Hu FB, Groop LC, Orho-Melander M, Ekelund U, Franks PW, Loos RJ (2011a) Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children. PLoS Med 8(11):e1001116PubMedCentralPubMedGoogle Scholar
  94. Kilpeläinen TO, Zillikens MC, Stančákova A, Finucane FM, Ried JS, Langenberg C, Zhang W, Beckmann JS, Luan J, Vandenput L, Styrkarsdottir U, Zhou Y, Smith AV, Zhao JH, Amin N, Vedantam S, Shin SY, Haritunians T, Fu M, Feitosa MF, Kumari M, Halldorsson BV, Tikkanen E, Mangino M, Hayward C, Song C, Arnold AM, Aulchenko YS, Oostra BA, Campbell H, Cupples LA, Davis KE, Döring A, Eiriksdottir G, Estrada K, Fernández-Real JM, Garcia M, Gieger C, Glazer NL, Guiducci C, Hofman A, Humphries SE, Isomaa B, Jacobs LC, Jula A, Karasik D, Karlsson MK, Khaw KT, Kim LJ, Kivimäki M, Klopp N, Kühnel B, Kuusisto J, Liu Y, Ljunggren O, Lorentzon M, Luben RN, McKnight B, Mellström D, Mitchell BD, Mooser V, Moreno JM, Männistö S, O’Connell JR, Pascoe L, Peltonen L, Peral B, Perola M, Psaty BM, Salomaa V, Savage DB, Semple RK, Skaric-Juric T, Sigurdsson G, Song KS, Spector TD, Syvänen AC, Talmud PJ, Thorleifsson G, Thorsteinsdottir U, Uitterlinden AG, van Duijn CM, Vidal-Puig A, Wild SH, Wright AF, Clegg DJ, Schadt E, Wilson JF, Rudan I, Ripatti S, Borecki IB, Shuldiner AR, Ingelsson E, Jansson JO, Kaplan RC, Gudnason V, Harris TB, Groop L, Kiel DP, Rivadeneira F, Walker M, Barroso I, Vollenweider P, Waeber G, Chambers JC, Kooner JS, Soranzo N, Hirschhorn JN, Stefansson K, Wichmann HE, Ohlsson C, O’Rahilly S, Wareham NJ, Speliotes EK, Fox CS, Laakso M, Loos RJ (2011b) Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile. Nat Genet 43:753–760PubMedCentralPubMedGoogle Scholar
  95. Kim JK, Samaranayake M, Pradhan S (2009) Epigenetic mechanisms in mammals. Cell Mol Life Sci 66(4):596–612PubMedCentralPubMedGoogle Scholar
  96. Kimura M (1983) The neutral theory of molecular evolution. Cambridge University Press, CambridgeGoogle Scholar
  97. Klöting N, Berthold S, Kovacs P, Schön MR, Fasshauer M, Ruschke K, Stumvoll M, Blüher M (2009) MicroRNA expression in human omental and subcutaneous adipose tissue. PLoS ONE 4:e4699PubMedCentralPubMedGoogle Scholar
  98. Knowler WC, Pettitt DJ, Saad MF, Bennett PH (1990) Diabetes mellitus in the Pima Indians: incidence, risk factors and pathogenesis. Diabetes Metab Rev 6(1):1–27PubMedGoogle Scholar
  99. Kucharski R, Maleszka J, Foret S, Maleszka R (2008) Nutritional control of reproductive status in honeybees via DNA methylation. Science 319:1827–1830PubMedGoogle Scholar
  100. Kuzawa C, Sweet E (2009) Epigenetics and the embodiment of race: developmental origins of US racial disparities in cardiovascular health. Am J Hum Biol 21:2–15PubMedGoogle Scholar
  101. Lavie CJ, De Schutter A, Milani RV (2015) Healthy obese versus unhealthy lean: the obesity paradox. Nat Rev Endocrinol 11(1):55–62PubMedGoogle Scholar
  102. Lee IM, Djoussé L, Sesso HD, Wang L, Buring JE (2010) Physical activity and weight gain prevention. JAMA 303(12):1173–1179PubMedCentralPubMedGoogle Scholar
  103. León-Mimila P, Villamil-Ramírez H, Villalobos-Comparán M, Villarreal-Molina T, Romero-Hidalgo S, López-Contreras B, Gutiérrez-Vidal R, Vega-Badillo J, Jacobo-Albavera L, Posadas-Romeros C, Canizalez-Román A, Río-Navarro BD, Campos-Pérez F, Acuña-Alonzo V, Aguilar-Salinas C, Canizales-Quinteros S (2013) Contribution of common genetic variants to obesity and obesity-related traits in Mexican children and adults. PLoS ONE 8(8):e70640PubMedCentralPubMedGoogle Scholar
  104. Li S, Zhao JH, Luan J, Luben RN, Rodwell SA, Khaw KT, Ong KK, Wareham NJ, Loos RJ (2010) Cumulative effects and predictive value of common obesity-susceptibility variants identified by genome-wide association studies. Am J Clin Nutr 91(1):184–190PubMedGoogle Scholar
  105. Lindgren CM, Heid IM, Randall JC, Lamina C, Steinthorsdottir V, Qi L, Speliotes EK, Thorleifsson G, Willer CJ, Herrera BM, Jackson AU, Lim N, Scheet P, Soranzo N, Amin N, Aulchenko YS, Chambers JC, Drong A, Luan J, Lyon HN, Rivadeneira F, Sanna S, Timpson NJ, Zillikens MC, Zhao JH, Almgren P, Bandinelli S, Bennett AJ, Bergman RN, Bonnycastle LL, Bumpstead SJ, Chanock SJ, Cherkas L, Chines P, Coin L, Cooper C, Crawford G, Doering A, Dominiczak A, Doney AS, Ebrahim S, Elliott P, Erdos MR, Estrada K, Ferrucci L, Fischer G, Forouhi NG, Gieger C, Grallert H, Groves CJ, Grundy S, Guiducci C, Hadley D, Hamsten A, Havulinna AS, Hofman A, Holle R, Holloway JW, Illig T, Isomaa B, Jacobs LC, Jameson K, Jousilahti P, Karpe F, Kuusisto J, Laitinen J, Lathrop GM, Lawlor DA, Mangino M, McArdle WL, Meitinger T, Morken MA, Morris AP, Munroe P, Narisu N, Nordström A, Nordström P, Oostra BA, Palmer CN, Payne F, Peden JF, Prokopenko I, Renström F, Ruokonen A, Salomaa V, Sandhu MS, Scott LJ, Scuteri A, Silander K, Song K, Yuan X, Stringham HM, Swift AJ, Tuomi T, Uda M, Vollenweider P, Waeber G, Wallace C, Walters GB, Weedon MN, Wellcome Trust Case Control Consortium, Witteman JC, Zhang C, Zhang W, Caulfield MJ, Collins FS, Davey Smith G, Day IN, Franks PW, Hattersley AT, Hu FB, Jarvelin MR, Kong A, Kooner JS, Laakso M, Lakatta E, Mooser V, Morris AD, Peltonen L, Samani NJ, Spector TD, Strachan DP, Tanaka T, Tuomilehto J, Uitterlinden AG, van Duijn CM, Wareham NJ, Watkins H, Procardis Consortia, Waterworth DM, Boehnke M, Deloukas P, Groop L, Hunter DJ, Thorsteinsdottir U, Schlessinger D, Wichmann HE, Frayling TM, Abecasis GR, Hirschhorn JN, Loos RJ, Stefansson K, Mohlke KL, Barroso I, McCarthy MI, Giant Consortium (2009) Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution. PLoS Genet 5:e1000508PubMedCentralPubMedGoogle Scholar
  106. Llewellyn CH, Trzaskowski M, Plomin R, Wardle J (2013) Finding the missing heritability in pediatric obesity: the contribution of genome-wide complex trait analysis. Int J Obes (Lond) 37(11):1506–1509Google Scholar
  107. Loos RJ, Lindgren CM, Li S, Wheeler E, Zhao JH, Prokopenko I, Inouye M, Freathy RM, Attwood AP, Beckmann JS, Berndt SI, Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, Jacobs KB, Chanock SJ, Hayes RB, Bergmann S, Bennett AJ, Bingham SA, Bochud M, Brown M, Cauchi S, Connell JM, Cooper C, Smith GD, Day I, Dina C, De S, Dermitzakis ET, Doney AS, Elliott KS, Elliott P, Evans DM, Sadaf Farooqi I, Froguel P, Ghori J, Groves CJ, Gwilliam R, Hadley D, Hall AS, Hattersley AT, Hebebrand J, KORA, Heid IM, Lamina C, Gieger C, Illig T, Meitinger T, Wichmann HE, Herrera B, Hinney A, Hunt SE, Jarvelin MR, Johnson T, Jolley JD, Karpe F, Keniry A, Khaw KT, Luben RN, Mangino M, Marchini J, McArdle WL, McGinnis R, Meyre D, Munroe PB, Morris AD, Ness AR, Neville MJ, Nica AC, Ong KK, O’Rahilly S, Owen KR, Palmer CN, Papadakis K, Potter S, Pouta A, Qi L, Nurses’ Health Study, Randall JC, Rayner NW, Ring SM, Sandhu MS, Scherag A, Sims MA, Song K, Soranzo N, Speliotes EK, Diabetes Genetics Initiative, Syddall HE, Teichmann SA, Timpson NJ, Tobias JH, Uda M, SardiNIA Study, Vogel CI, Wallace C, Waterworth DM, Weedon MN, Welcome Trust Case Control Consortium, Willer CJ, FUSION, Wraight, Yuan X, Zeggini E, Hirschhorn JN, Strachan DP, Ouwehand WH, Caulfield MJ, Samani NJ, Frayling TM, Vollenweider P, Waeber G, Mooser V, Deloukas P, McCarthy MI, Wareham NJ, Barroso I, Jacobs KB, Chanock SJ, Hayes RB, Lamina C, Gieger C, Illig T, Meitinger T, Wichmann HE, Kraft P, Hankinson SE, Hunter DJ, Hu FB, Lyon HN, Voight BF, Ridderstrale M, Groop L, Scheet P, Sanna S, Abecasis GR, Albai G, Nagaraja R, Schlessinger D, Jackson AU, Tuomilehto J, Collins FS, Boehnke M, Mohlke KL (2008) Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat Genet 40(6):768–775PubMedCentralPubMedGoogle Scholar
  108. Loos RJ, Yeo GSH (2014) The bigger picture of FTO—the first GWAS-identified obesity gene. Nat Rev Endocrinol 10(1):51–61PubMedCentralPubMedGoogle Scholar
  109. Loos RJ, Rankinen T, Tremblay A, Perusse L, Chagnon Y, Bouchard C (2005) Melanocortin-4 receptor gene and physical activity in the Quebec Family Study. Int J Obes (Lond) 29:420–428Google Scholar
  110. Loss RJ (2012) Genetic determinants of common obesity and their value in prediction. Best Pract Res Clin Endocrinol Metab 26:211–226Google Scholar
  111. Lutz T, Woods S (2012) Overview of animal models of obesity. Curr Protoc Pharmacol 5:61PubMedGoogle Scholar
  112. Mačeková S, Bernasovský I, Gabriková D, Bôžiková A, Bernasovská J, Boroňová I, Behulová R, Svíčková P, Petrejčíková E, Soták M, Sovičová A, Carnogurská J (2012) Association of the FTO rs9939609 polymorphism with obesity in Roma/Gypsy population. Am J Phys Anthropol 147(1):30–34PubMedGoogle Scholar
  113. Magnusson PK, Rasmussen F (2002) Familial resemblance of body mass index and familial risk of high and low body mass index. A study of young men in Sweden. Int J Obes Relat Metab Disord 26:1225–1231PubMedGoogle Scholar
  114. Mamun AA, O´Callaghan M, Callaway L, Najman J, Lawlor DA DA (2009) Associations of gestational weight gain with offspring body mass index and blood pressure at 21 years of age: evidence from a birth cohort study. Circulation 119:1720–1727PubMedGoogle Scholar
  115. Mardis ER (2013) Next-generation sequencing platforms. Annu Rev Anal Chem 6:287–303Google Scholar
  116. Marian AJ (2012) Molecular genetic studies of complex phenotypes. Transl Res 159(2):64–79PubMedCentralPubMedGoogle Scholar
  117. Mathes WF, Aylor DL, Miller DR, Churchill GA, Chesler EJ, de Villena FP, Threadgill DW, Pomp D (2011) Architecture of energy balance traits in emerging lines of the collaborative cross. Am J Physiol Endocrinol Metab 300(6):e1124–e1134PubMedCentralPubMedGoogle Scholar
  118. McKay J, Mathers J (2011) Diet induced epigenetic changes and their implications for health. Acta Physiol 202:103–118Google Scholar
  119. Milagro FI, Campión J, Garcia-Diaz DF, Goyenechea E, Paternain L, Martinez JÁ (2009) High fat diet-induced obesity modifies the methylation pattern of leptin promoter in rats. J Physiol Biochem 65:1–9PubMedGoogle Scholar
  120. Million M, Lagier JC, Yahav D, Paul M (2013) Gut bacterial microbiota and obesity. Clin Microbiol Infect 19(4):305–313PubMedGoogle Scholar
  121. Milner JA (2004) Molecular targets for bioactive food components. J Nutr 134(9):2492S–2498SPubMedGoogle Scholar
  122. Mitchell JA, Hakonarson H, Rebbeck TR, Grant SF (2013) Obesity-susceptibility loci and the tails of the pediatric BMI distribution. Obesity 21:1256–1260PubMedCentralPubMedGoogle Scholar
  123. Monda KL, Chen GK, Taylor KC, Palmer C, Edwards TL, Lange LA, Ng MC, Adeyemo AA, Allison MA, Bielak LF, Chen G, Graff M, Irvin MR, Rhie SK, Li G, Liu Y, Liu Y, Lu Y, Nalls MA, Sun YV, Wojczynski MK, Yanek LR, Aldrich MC, Ademola A, Amos CI, Bandera EV, Bock CH, Britton A, Broeckel U, Cai Q, Caporaso NE, Carlson CS, Carpten J, Casey G, Chen WM, Chen F, Chen YD, Chiang CW, Coetzee GA, Demerath E, Deming-Halverson SL, Driver RW, Dubbert P, Feitosa MF, Feng Y, Freedman BI, Gillanders EM, Gottesman O, Guo X, Haritunians T, Harris T, Harris CC, Hennis AJ, Hernandez DG, McNeill LH, Howard TD, Howard BV, Howard VJ, Johnson KC, Kang SJ, Keating BJ, Kolb S, Kuller LH, Kutlar A, Langefeld CD, Lettre G, Lohman K, Lotay V, Lyon H, Manson JE, Maixner W, Meng YA, Monroe KR, Morhason-Bello I, Murphy AB, Mychaleckyj JC, Nadukuru R, Nathanson KL, Nayak U, N’diaye A, Nemesure B, Wu SY, Leske MC, Neslund-Dudas C, Neuhouser M, Nyante S, Ochs-Balcom H, Ogunniyi A, Ogundiran TO, Ojengbede O, Olopade OI, Palmer JR, Ruiz-Narvaez EA, Palmer ND, Press MF, Rampersaud E, Rasmussen-Torvik LJ, Rodriguez-Gil JL, Salako B, Schadt EE, Schwartz AG, Shriner DA, Siscovick D, Smith SB, Wassertheil-Smoller S, Speliotes EK, Spitz MR, Sucheston L, Taylor H, Tayo BO, Tucker MA, Van Den Berg DJ, Edwards DR, Wang Z, Wiencke JK, Winkler TW, Witte JS, Wrensch M, Wu X, Yang JJ, Levin AM, Young TR, Zakai NA, Cushman M, Zanetti KA, Zhao JH, Zhao W, Zheng Y, Zhou J, Ziegler RG, Zmuda JM, Fernandes JK, Gilkeson GS, Kamen DL, Hunt KJ, Spruill IJ, Ambrosone CB, Ambs S, Arnett DK, Atwood L, Becker DM, Berndt SI, Bernstein L, Blot WJ, Borecki IB, Bottinger EP, Bowden DW, Burke G, Chanock SJ, Cooper RS, Ding J, Duggan D, Evans MK, Fox C, Garvey WT, Bradfield JP, Hakonarson H, Grant SF, Hsing A, Chu L, Hu JJ, Huo D, Ingles SA, John EM, Jordan JM, Kabagambe EK, Kardia SL, Kittles RA, Goodman PJ, Klein EA, Kolonel LN, Le Marchand L, Liu S, McKnight B, Millikan RC, Mosley TH, Padhukasahasram B, Williams LK, Patel SR, Peters U, Pettaway CA, Peyser PA, Psaty BM, Redline S, Rotimi CN, Rybicki BA, Sale MM, Schreiner PJ, Signorello LB, Singleton AB, Stanford JL, Strom SS, Thun MJ, Vitolins M, Zheng W, Moore JH, Williams SM, Ketkar S, Zhu X, Zonderman AB, NABEC Consortium; UKBEC Consortium; BioBank Japan Project; AGEN Consortium, Kooperberg C, Papanicolaou GJ, Henderson BE, Reiner AP, Hirschhorn JN, Loos RJ, North KE, Haiman CA (2013) A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry. Nat Genet 45(6):690–696PubMedCentralPubMedGoogle Scholar
  124. Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H, Wareham NJ, Sewter CP, Digby JE, Mohammed SN, Hurst JA, Cheetham CH, Earley AR, Barnett AH, Prins JB, O’Rahilly S (1997) Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 387:903–908PubMedGoogle Scholar
  125. Moore LL, Lombardi DA, White MJ, Campbell JL, Oliveria SA, Ellison RC (1991) Influence of parents’ physical activity levels on activity levels of young children. J Pediatr 118:215–219PubMedGoogle Scholar
  126. Mountjoy KG, Mortrud MT, Low MJ, Simerly RB, Cone RD (1994) Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain. Mol Endocrinol 8:1298–1308PubMedGoogle Scholar
  127. Mutch DM, Clément K (2006) Unravelling the genetics of human obesity. PLoS Genet 2:e188PubMedCentralPubMedGoogle Scholar
  128. Myles S, Lea RA, Ohashi J, Chambers GK, Weiss JG, Hardouin E, Engelken J, Macartney-Coxson DP, Eccles DA, Naka I, Kimura R, Inaoka T, Matsumura Y, Stoneking M (2011) Testing the thrifty gene hypothesis: the Gly482Ser variant in PPARGC1A is associated with BMI in tongans. BMC Med Genet 12:10PubMedCentralPubMedGoogle Scholar
  129. Nakayama K, Ogawa A, Miyashita H, Tabara Y, Igase M, Kohara K, Miki T, Kagawa Y, Yanagisawa Y, Katashima M, Onda T, Okada K, Fukushima S, Iwamoto S (2013) Positive natural selection of TRIB2, a novel gene that influences visceral fat accumulation East Asia. Hum Genet 132(2):201–217PubMedGoogle Scholar
  130. Neel JV (1962) Diabetes mellitus: a “thrifty” genotype rendered detrimental by “progress”? Bull WHO 77(8):694–703Google Scholar
  131. Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, Mullany EC, Biryukov S, Abbafati C, Abera SF, Abraham JP, Abu-Rmeileh NM, Achoki T, AlBuhairan FS, Alemu ZA, Alfonso R, Ali MK, Ali R, Guzman NA, Ammar W, Anwari P, Banerjee A, Barquera S, Basu S, Bennett DA, Bhutta Z, Blore J, Cabral N, Nonato IC, Chang JC, Chowdhury R, Courville KJ, Criqui MH, Cundiff DK, Dabhadkar KC, Dandona L, Davis A, Dayama A, Dharmaratne SD, Ding EL, Durrani AM, Esteghamati A, Farzadfar F, Fay DF, Feigin VL, Flaxman A, Forouzanfar MH, Goto A, Green MA, Gupta R, Hafezi-Nejad N, Hankey GJ, Harewood HC, Havmoeller R, Hay S, Hernandez L, Husseini A, Idrisov BT, Ikeda N, Islami F, Jahangir E, Jassal SK, Jee SH, Jeffreys M, Jonas JB, Kabagambe EK, Khalifa SE, Kengne AP, Khader YS, Khang YH, Kim D, Kimokoti RW, Kinge JM, Kokubo Y, Kosen S, Kwan G, Lai T, Leinsalu M, Li Y, Liang X, Liu S, Logroscino G, Lotufo PA, Lu Y, Ma J, Mainoo NK, Mensah GA, Merriman TR, Mokdad AH, Moschandreas J, Naghavi M, Naheed A, Nand D, Narayan KM, Nelson EL, Neuhouser ML, Nisar MI, Ohkubo T, Oti SO, Pedroza A, Prabhakaran D, Roy N, Sampson U, Seo H, Sepanlou SG, Shibuya K, Shiri R, Shiue I, Singh GM, Singh JA, Skirbekk V, Stapelberg NJ, Sturua L, Sykes BL, Tobias M, Tran BX, Trasande L, Toyoshima H, van de Vijver S, Vasankari TJ, Veerman JL, Velasquez-Melendez G, Vlassov VV, Vollset SE, Vos T, Wang C, Wang X, Weiderpass E, Werdecker A, Wright JL, Yang YC, Yatsuya H, Yoon J, Yoon SJ, Zhao Y, Zhou M, Zhu S, Lopez AD, Murray CJ, Gakidou E (2014) Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 384(9945):766–781PubMedGoogle Scholar
  132. Nielsen R (2005) Molecular signatures of natural selection. Annu Rev Genet 39:197–218PubMedGoogle Scholar
  133. Ntalla I, Panoutsopoulou K, Vlachou P, Southam L, William Rayner N, Zeggini E, Dedoussis GV (2013) Replication of established common genetic variants for adult BMI and childhood obesity in Greek adolescents: The TEENAGE Study. Ann Hum Genet 77(3):268–274PubMedCentralPubMedGoogle Scholar
  134. O'Connor A, Swick A (2013) Interface between pharmacotherapy and genes in human obesity. Hum Hered 75:116–126PubMedGoogle Scholar
  135. Ohashi J, Naka I, Kimura R, Natsuhara K, Yamauchi T, Furusawa T, Nakazawa M, Ataka Y, Patarapotikul J, Nuchnoi P, Tokunaga K, Ishida T, Inaoka T, Matsumura Y, Ohtsuka R (2007) FTO polymorphisms in oceanic populations. J Hum Genet 52:1031–1035PubMedGoogle Scholar
  136. O’Rahilly S, Farooqi SI (2008) Human obesity: a heritable neurobehavioral disorder that is highly sensitive to environmental conditions. Diabetes 57(11):2905–2910PubMedCentralPubMedGoogle Scholar
  137. Ortega FJ, Moreno-Navarrete JM, Pardo G, Sabater M, Hummel M, Ferrer A, Rodriguez-Hermosa JI, Ruiz B, Ricart W, Peral B, Fernández-Real JM (2010) MiRNA expression profile of human subcutaneous adipose and during adipocyte differentiation. PLoS ONE 5:e9022PubMedCentralPubMedGoogle Scholar
  138. Ortega FJ, Mercader JM, Catalán V, Moreno-Navarrete JM, Pueyo N, Sabater M, Gómez-Ambrosi J, Anglada R, Fernández-Formoso JA, Ricart W, Frühbeck G, Fernández-Real JM (2013) Targeting the circulating MicroRNA signature of obesity. Clin Chem 59(5):781–792PubMedGoogle Scholar
  139. Ortega-Azorín C, Sorlí JV, Asensio EM, Coltell O, Martínez-González MÁ, Salas-Salvadó J, Covas MI, Arós F, Lapetra J, Serra-Majem L, Gómez-Gracia E, Fiol M, Sáez-Tormo G, Pintó X, Muñoz MA, Ros E, Ordovás JM, Estruch R, Corella D (2012) Associations of the FTO rs9939609 and the MC4R rs17782313 polymorphisms with type 2 diabetes are modulated by diet, being higher when adherence to the Mediterranean diet pattern is low. Cardiovasc Diabetol 11:137PubMedCentralPubMedGoogle Scholar
  140. Peters T, Ausmeier K, Dildrop R, Rüther U (2002) The mouse fused toes (Ft) mutation is the result of a 1.6-Mb deletion including the entire Iroquois B gene cluster. Mamm Genome 13(4):186–188PubMedGoogle Scholar
  141. Peters U, North KE, Sethupathy P, Buyske S, Haessler J, Jiao S, Fesinmeyer MD, Jackson RD, Kuller LH, Rajkovic A, Lim U, Cheng I, Schumacher F, Wilkens L, Li R, Monda K, Ehret G, Nguyen KD, Cooper R, Lewis CE, Leppert M, Irvin MR, Gu CC, Houston D, Buzkova P, Ritchie M, Matise TC, Le Marchand L, Hindorff LA, Crawford DC, Haiman CA, Kooperberg C (2013) A systematic mapping approach of 16q12.2/FTO and BMI in more than 20,000 African Americans narrows in on the underlying functional variation: results from the Population Architecture using Genomics and Epidemiology (PAGE) study. PLoS Genet 9(1):e1003171PubMedCentralPubMedGoogle Scholar
  142. Qi Q, Chu AY, Kang JH, Jensen MK, Curhan GC, Pasquale LR, Ridker PM, Hunter DJ, Willett WC, Rimm EB, Chasman DI, Hu FB, Qi L (2012) Sugar-sweetened beverages and genetic risk of obesity. N Eng J Med 367:1387–1396Google Scholar
  143. Rampersaud E, Mitchell BD, Pollin TI, Fu M, Shen H, O'Connell JR, Ducharme JL, Hines S, Sack P, Naglieri R, Shuldiner AR, Snitker S (2008) Physical activity and the association of common FTO gene variants with body mass index and obesity. Arch Intern Med 168(16):1791–1797PubMedCentralPubMedGoogle Scholar
  144. Ranadive SA, Vaisse C (2008) Lessons from extreme human obesity: monogenic disorders. Endocrinol Metab Clin North Am 37(3):733–751PubMedGoogle Scholar
  145. Rankinen T, Zuberi A, Chagnon YC, Weisnagel SJ, Argyropoulos G, Walts B, Pérusse L, Bouchard C (2006) The human obesity gene map: the 2005 update. Obesity (Silver Spring) 14:529–644Google Scholar
  146. Rau H, Reaves BJ, O’Rahilly S, Whitehead JP (1999) Truncated human leptin (delta133) associated with extreme obesity undergoes proteasomal degradation after defective intracellular transport. Endocrinology 140:1718–1723PubMedGoogle Scholar
  147. Ravussin E, Bouchard C (2000) Human genomics and obesity: finding appropriate drug targets. Eur J Pharmacol 410(2–3):131–145PubMedGoogle Scholar
  148. Razquin C, Marti A, Martinez JA (2011) Evidences on three relevant obesogenes: MC4R, FTO and PPARγ. Approaches for personalized nutrition. Mol Nutr Food Res 55:136–149PubMedGoogle Scholar
  149. Relton CL, Groom A, St Pourcain B, Sayers AE, Swan DC, Embleton ND, Pearce MS, Ring SM, Northstone K, Tobias JH, Trakalo J, Ness AR, Shaheen SO, Davey Smith G (2012) DNA methylation patterns in cord blood DNA and body size in childhood. PLoS ONE 7:e31821PubMedCentralPubMedGoogle Scholar
  150. Rey D, Fernandez-Honrado M, Areces C, Algora M, Abd-El-Fatah-Khalil S, Enriquez-de-Salamanca M, Coca C, Arribas I, Arnaiz-Villena A (2012) Amerindians show no association of PC-1 gene Gln121 allele and obesity: a thrifty gene population genetics. Mol Biol Rep 39(7):7687–7693PubMedGoogle Scholar
  151. Richardson AS, North KE, Graff M, Young KM, Mohlke KL, Lange LA, Lange EM, Harris KM, Gordon-Larsen P (2014) Moderate to vigorous physical activity interactions with genetic variants and body mass index in a large US ethnically diverse cohort. Pediatric Obesity 9(2):e35–e46PubMedCentralPubMedGoogle Scholar
  152. Rinella E, Still C, Shao Y, Wood GC, Chu X, Salerno B, Gerhard GS, Ostrer H (2013) Genome-wide association of single-nucleotide polymorphisms with weight loss outcomes after roux-en-Y gastric bypass surgery. J Clin Endocrinol Metab 98(6):E1131–E1136PubMedCentralPubMedGoogle Scholar
  153. Rodríguez-López R, González-Carpio M, Serrano MV, Torres G, García de Cáceres MT, Herrera T, Román A, Rubio M, Méndez P, Hernández-Sáez R, Núñez M, Luengo LM (2010) Association of FTO gene polymorphisms and morbid obesity in the population of extremadura. Endocrinol Nutr 57(5):203–209PubMedGoogle Scholar
  154. Romero-Corral A, Montori VM, Somers VK, Korinek J, Thomas RJ, Allison TG, Mookadam F, Lopez-Jimenez F (2006) Association of bodyweight with total mortality and with cardiovascular events in coronary artery disease: a systematic review of cohort studies. Lancet 368(9536):666–678PubMedGoogle Scholar
  155. Rönn T, Volkov P, Davegårdh C, Dayeh T, Hall E, Olsson AH, Nilsson E, Tornberg A, Dekker Nitert M, Eriksson KF, Jones HA, Groop L, Ling C (2013) A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue. PLoS Genet 9(6):e1003572PubMedCentralPubMedGoogle Scholar
  156. Ruiz JR, Labayen I, Ortega FB, Legry V, Moreno LA, Dallongeville J, Martínez-Gómez D, Bokor S, Manios Y, Ciarapica D, Gottrand F, De Henauw S, Molnár D, Sjöström M, Meirhaeghe A; HELENA Study Group (2010) Attenuation of the effect of the FTO rs9939609 polymorphism on total and central body fat by physical activity in adolescents: the HELENA study. Arch Pediatr Adolesc Med 164(4):328–333PubMedGoogle Scholar
  157. Saeed S, Bonnefond A, Manzoor J, Philippe J, Durand E, Arshad M, Sand O, Butt TA, Falchi M, Arslan M, Froguel P (2014) Novel LEPR mutations in obese Pakistani children identified by PCR-based enrichment and next generation sequencing. Obesity (Silver Spring) 22(4):1112–1117Google Scholar
  158. Sällman Almén M, Rask-Andersen M, Jacobsson JA, Ameur A, Kalnina I, Moschonis G, Juhlin S, Bringeland N, Hedberg LA, Ignatovica V, Chrousos GP, Manios Y, Klovins J, Marcus C, Gyllensten U, Fredriksson R, Schiöth HB (2013) Determination of the obesity-associated gene variants within the entire FTO gene by ultra-deep targeted sequencing in obese and lean children. Int J Obes (Lond) 37(3):424–431Google Scholar
  159. Sandholt CH, Hansen T, Pedersen O (2012) Beyond the fourth wave of genome-wide obesity association studies. Nutr Diabetes 2:e37PubMedCentralPubMedGoogle Scholar
  160. Scuteri A, Sanna S, Chen WM, Uda M, Albai G, Strait J, Najjar S, Nagaraja R, Orrú M, Usala G, Dei M, Lai S, Maschio A, Busonero F, Mulas A, Ehret GB, Fink AA, Weder AB, Cooper RS, Galan P, Chakravarti A, Schlessinger D, Cao A, Lakatta E, Abecasis GR (2007) Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet 3(7):1200–1210Google Scholar
  161. Sellayah D, Cagampang FR, Cox RD (2014) On the evolutionary origins of obesity: a new hypothesis. Endocrinology 155(5):1573–1588PubMedGoogle Scholar
  162. Sevilla S, Hubal MJ (2014) Genetic modifiers of obesity and bariatric surgery outcomes. Semin Pediatr Surg 23(1):43–48PubMedGoogle Scholar
  163. Silventoinen K, Rokholm B, Kaprio J, Sørensen TI (2010) The genetic and environmental influences on childhood obesity: a systematic review of twin and adoption studies. Int J Obes 34(1):29–40Google Scholar
  164. Slatkin M (2008) Linkage disequilibrium-understanding the evolutionary past and mapping the medical future. Nat Rev 9(6):477–485Google Scholar
  165. Smemo S, Tena JJ, Kim KH (2014) Obesity-associated variants within FTO form long-range functional connections with IRX3. Nature 507(7492):371–375PubMedCentralPubMedGoogle Scholar
  166. Song Y, You NC, Hsu YH, Howard BV, Langer RD, Manson JE, Nathan L, Niu T, Tinker F, Liu LS (2008) FTO polymorphisms are associated with obesity but not diabetes risk in postmenopausal women. Obesity (Silver Spring) 16(11):2472–2480PubMedCentralGoogle Scholar
  167. Soubry A, Schildkraut JM, Murtha A, Wang F, Huang Z, Bernal A, Kurtzberg J, Jirtle RL, Murphy SK, Hoyo C (2013a) Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort. BMC Med 11:29PubMedCentralPubMedGoogle Scholar
  168. Soubry A, Murphy SK, Wang F, Huang Z, Vidal AC, Fuemmeler BF, Kurtzberg J, Murtha A, Jirtle RL, Schildkraut JM, Hoyo C (2013b) Newborns of obese parents have altered DNA methylation patterns at imprinted genes. Int J Obes (Lond). doi: 10.1038/ijo.2013.193 [Epub ahead of print]
  169. Sovio U, Mook-Kanamori DO, Warrington NM, Lawrence R, Briollais L, Palmer CN, Cecil J, Sandling JK, Syvänen AC, Kaakinen M, Beilin LJ, Millwood IY, Bennett AJ, Laitinen J, Pouta A, Molitor J, Davey Smith G, Ben-Shlomo Y, Jaddoe VW, Palmer LJ, Pennell CE, Cole TJ, McCarthy MI, Järvelin MR, Timpson NJ, Early Growth Genetics Consortium (2011) Association between common variation at the FTO locus and changes in body mass index from infancy to late childhood: the complex nature of genetic association through growth and development. PLoS Genet 7(2):e1001307PubMedCentralPubMedGoogle Scholar
  170. Speakman JR (2004) Obesity: the integrated roles of environment and genetics. J Nutrition 134:2090S–2105SGoogle Scholar
  171. Speakman JR (2006) Thrifty genes for obesity and the metabolic syndrome-time to call off the search? Diab Vasc Dis Res 3(1):7–11PubMedGoogle Scholar
  172. Speakman JR (2008) Thrifty genes for obesity, an attractive but flawed idea, and an alternative perspective: the ‘drifty gene’ hypothesis. Int J Obes (Lond) 32(11):1611–1617Google Scholar
  173. Speakman JR (2013) Evolutionary perspectives on the obesity epidemic: adaptive, maladaptive, and neutral viewpoints. Annu Rev Nutr 33:289–317PubMedGoogle Scholar
  174. Speakman JR, Rance KA, Johnstone AM (2008) Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure. Obesity (Silver Spring) 16:1961–1965Google Scholar
  175. Speliotes EK, Willer CJ, Berndt SI, Monda KL, Thorleifsson G, Jackson AU, Lango Allen H, Lindgren CM, Luan J, Mägi R, Randall JC, Vedantam S, Winkler TW, Qi L, Workalemahu T, Heid IM, Steinthorsdottir V, Stringham HM, Weedon MN, Wheeler E, Wood AR, Ferreira T, Weyant RJ, Segrè AV, Estrada K, Liang L, Nemesh J, Park JH, Gustafsson S, Kilpeläinen TO, Yang J, Bouatia-Naji N, Esko T, Feitosa MF, Kutalik Z, Mangino M, Raychaudhuri S, Scherag A, Smith AV, Welch R, Zhao JH, Aben KK, Absher DM, Amin N, Dixon AL, Fisher E, Glazer NL, Goddard ME, Heard-Costa NL, Hoesel V, Hottenga JJ, Johansson A, Johnson T, Ketkar S, Lamina C, Li S, Moffatt MF, Myers RH, Narisu N, Perry JR, Peters MJ, Preuss M, Ripatti S, Rivadeneira F, Sandholt C, Scott LJ, Timpson NJ, Tyrer JP, van Wingerden S, Watanabe RM, White CC, Wiklund F, Barlassina C, Chasman DI, Cooper MN, Jansson JO, Lawrence RW, Pellikka N, Prokopenko I, Shi J, Thiering E, Alavere H, Alibrandi MT, Almgren P, Arnold AM, Aspelund T, Atwood LD, Balkau B, Balmforth AJ, Bennett AJ, Ben-Shlomo Y, Bergman RN, Bergmann S, Biebermann H, Blakemore AI, Boes T, Bonnycastle LL, Bornstein SR, Brown MJ, Buchanan TA, Busonero F, Campbell H, Cappuccio FP, Cavalcanti-Proença C, Chen YD, Chen CM, Chines PS, Clarke R, Coin L, Connell J, Day IN, den Heijer M, Duan J, Ebrahim S, Elliott P, Elosua R, Eiriksdottir G, Erdos MR, Eriksson JG, Facheris MF, Felix SB, Fischer-Posovszky P, Folsom AR, Friedrich N, Freimer NB, Fu M, Gaget S, Gejman PV, Geus EJ, Gieger C, Gjesing AP, Goel A, Goyette P, Grallert H, Grässler J, Greenawalt DM, Groves CJ, Gudnason V, Guiducci C, Hartikainen AL, Hassanali N, Hall AS, Havulinna AS, Hayward C, Heath AC, Hengstenberg C, Hicks AA, Hinney A, Hofman A, Homuth G, Hui J, Igl W, Iribarren C, Isomaa B, Jacobs KB, Jarick I, Jewell E, John U, Jørgensen T, Jousilahti P, Jula A, Kaakinen M, Kajantie E, Kaplan LM, Kathiresan S, Kettunen J, Kinnunen L, Knowles JW, Kolcic I, König IR, Koskinen S, Kovacs P, Kuusisto J, Kraft P, Kvaløy K, Laitinen J, Lantieri O, Lanzani C, Launer LJ, Lecoeur C, Lehtimäki T, Lettre G, Liu J, Lokki ML, Lorentzon M, Luben RN, Ludwig B, MAGIC, Manunta P, Marek D, Marre M, Martin NG, McArdle WL, McCarthy A, McKnight B, Meitinger T, Melander O, Meyre D, Midthjell K, Montgomery GW, Morken MA, Morris AP, Mulic R, Ngwa JS, Nelis M, Neville MJ, Nyholt DR, O’Donnell CJ, O’Rahilly S, Ong KK, Oostra B, Paré G, Parker AN, Perola M, Pichler I, Pietiläinen KH, Platou CG, Polasek O, Pouta A, Rafelt S, Raitakari O, Rayner NW, Ridderstråle M, Rief W, Ruokonen A, Robertson NR, Rzehak P, Salomaa V, Sanders AR, Sandhu MS, Sanna S, Saramies J, Savolainen MJ, Scherag S, Schipf S, Schreiber S, Schunkert H, Silander K, Sinisalo J, Siscovick DS, Smit JH, Soranzo N, Sovio U, Stephens J, Surakka I, Swift AJ, Tammesoo ML, Tardif JC, Teder-Laving M, Teslovich TM, Thompson JR, Thomson B, Tönjes A, Tuomi T, van Meurs JB, van Ommen GJ, Vatin V, Viikari J, Visvikis-Siest S, Vitart V, Vogel CI, Voight BF, Waite LL, Wallaschofski H, Walters GB, Widen E, Wiegand S, Wild SH, Willemsen G, Witte DR, Witteman JC, Xu J, Zhang Q, Zgaga L, Ziegler A, Zitting P, Beilby JP, Farooqi IS, Hebebrand J, Huikuri HV, James AL, Kähönen M, Levinson DF, Macciardi F, Nieminen MS, Ohlsson C, Palmer LJ, Ridker PM, Stumvoll M, Beckmann JS, Boeing H, Boerwinkle E, Boomsma DI, Caulfield MJ, Chanock SJ, Collins FS, Cupples LA, Smith GD, Erdmann J, Froguel P, Grönberg H, Gyllensten U, Hall P, Hansen T, Harris TB, Hattersley AT, Hayes RB, Heinrich J, Hu FB, Hveem K, Illig T, Jarvelin MR, Kaprio J, Karpe F, Khaw KT, Kiemeney LA, Krude H, Laakso M, Lawlor DA, Metspalu A, Munroe PB, Ouwehand WH, Pedersen O, Penninx BW, Peters A, Pramstaller PP, Quertermous T, Reinehr T, Rissanen A, Rudan I, Samani NJ, Schwarz PE, Shuldiner AR, Spector TD, Tuomilehto J, Uda M, Uitterlinden A, Valle TT, Wabitsch M, Waeber G, Wareham NJ, Watkins H, Procardis Consortium, Wilson JF, Wright AF, Zillikens MC, Chatterjee N, McCarroll SA, Purcell S, Schadt EE, Visscher PM, Assimes TL, Borecki IB, Deloukas P, Fox CS, Groop LC, Haritunians T, Hunter DJ, Kaplan RC, Mohlke KL, O’Connell JR, Peltonen L, Schlessinger D, Strachan DP, van Duijn CM, Wichmann HE, Frayling TM, Thorsteinsdottir U, Abecasis GR, Barroso I, Boehnke M, Stefansson K, North KE, McCarthy MI, Hirschhorn JN, Ingelsson E, Loos RJ (2010) Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet 42(11):937–948PubMedCentralPubMedGoogle Scholar
  176. Steemburgo T, Azevedo MJ, Martínez JÁ (2009) Gene-nutrient interaction and its association with obesity and diabetes mellitus. Arq Bras Endocrinol Metabol 53(5):497–508PubMedGoogle Scholar
  177. Steemburgo T, Azevedo MJ, Gross JL, Milagro FI, Campión J, Martínez JÁ (2013) The rs9939609 polymorphism in the FTO gene is associated with fat and fiber intakes in patients with type 2 diabetes. J Nutrigenet Nutrigenomics 6(2):97–106PubMedGoogle Scholar
  178. Stefan N, Vozarova B, Del Parigi A, Ossowski V, Thompson DB, Hanson RL, Ravussin E, Tataranni PA (2002) The Gln223Arg polymorphism of the leptin receptor in Pima Indians: influence on energy expenditure, physical activity and lipid metabolism. Int J Obes Relat Metab Disord 26:1629–1632PubMedGoogle Scholar
  179. Still CD, Wood GC, Chu X, Erdman R, Manney CH, Benotti PN, Petrick AT, Strodel WE, Mirshahi UL, Mirshahi T, Carey DJ, Gerhard GS (2011) High allelic burden of four obesity SNPs is associated with poorer weight loss outcomes following gastric bypass surgery. Obesity (Silver Spring) 19(8):1676–1683Google Scholar
  180. Strobel A, Issad T, Camoin L, Ozata M, Strosberg AD (1998) A leptin missense mutation associated with hypogonadism and morbid obesity. Nat Genet 18:213–215PubMedGoogle Scholar
  181. Stunkard AJ, Foch TT, Hrubec Z (1986a) A twin study of human obesity. JAMA 256(1):51–54PubMedGoogle Scholar
  182. Stunkard AJ, Sorensen TI, Hanis C, Teasdale TW, Chakraborty R, Schull WJ, Schulsinger F (1986b) An adoption study of human obesity. N Engl J Med 314(4):193–198PubMedGoogle Scholar
  183. Swinburn BA, Sacks G, Hall KD, McPherson K, Finegood DT, Moodie ML, Gortmaker SL (2011) The global obesity pandemic: shaped by global drivers and local environments. Lancet 378(9793):804–814PubMedGoogle Scholar
  184. Takanabe R, Ono K, Abe Y, Takaya T, Horie T, Wada H, Kita T, Satoh N, Shimatsu A, Hasegawa K (2008) Up-regulated expression of microRNA-143 in association with obesity in adipose tissue of mice fed high-fat diet. Biochem Biophys Res Commun 376:728–732PubMedGoogle Scholar
  185. Tan LJ, Zhu H, He H, Wu KH, Li J, Chen XD, Zhang JG, Shen H, Tian Q, Krousel-Wood M, Papasian CJ, Bouchard C, Pérusse L, Deng HW (2014) Replication of 6 obesity genes in a meta-analysis of genome-wide association studies from diverse ancestries. PLoS ONE 9(5):e96149PubMedCentralPubMedGoogle Scholar
  186. Thorleifsson G, Walters GB, Gudbjartsson DF, Steinthorsdottir V, Sulem P, Helgadottir A, Styrkarsdottir U, Gretarsdottir S, Thorlacius S, Jonsdottir I, Jonsdottir T, Olafsdottir EJ, Olafsdottir GH, Jonsson T, Jonsson F, Borch-Johnsen K, Hansen T, Andersen G, Jorgensen T, Lauritzen T, Aben KK, Verbeek AL, Roeleveld N, Kampman E, Yanek LR, Becker LC, Tryggvadottir L, Rafnar T, Becker DM, Gulcher J, Kiemeney LA, Pedersen O, Kong A, Thorsteinsdottir U, Stefansson K (2009) Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat Genet 42(11):937–948Google Scholar
  187. Vaisse C, Clément K, Guy-Grand B, Froguel P (1998) A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nat Genet 20:113–114PubMedGoogle Scholar
  188. van den Born E, Omelchenko MV, Bekkelund A, Leihne V, Koonin EV, Dolja VV, Falnes PØ (2008) Viral AlkB proteins repair RNA damage by oxidative demethylation. Nucl Acids Res 36:5451–5461PubMedCentralPubMedGoogle Scholar
  189. Vu L, Switzer NJ, De Gara C, Karmali S (2013) Surgical interventions for obesity and metabolic disease. Best Pract Res Clin Endocrinol Metab 27(2):239–246PubMedGoogle Scholar
  190. Wang X, Zhu H, Snieder H, Su S, Munn D, Harshfield G, Maria BL, Dong Y, Treiber F, Gutin B, Shi H (2010) Obesity related methylation changes in DNA of peripheral blood leukocytes. BMC Med 8:87PubMedCentralPubMedGoogle Scholar
  191. Waterland RA, Jirtle RL (2003) Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol 23:5293–5300PubMedCentralPubMedGoogle Scholar
  192. Waters AM, Beales PL (2011) Ciliopathies: an expanding disease spectrum. Pediatr Nephrol 26:1039–1056PubMedCentralPubMedGoogle Scholar
  193. Wen W, Cho YS, Zheng W, Dorajoo R, Kato N, Qi L, Chen CH, Delahanty RJ, Okada Y, Tabara Y, Gu D, Zhu D, Haiman CA, Mo Z, Gao YT, Saw SM, Go MJ, Takeuchi F, Chang LC, Kokubo Y, Liang J, Hao M, Le Marchand L, Zhang Y, Hu Y, Wong TY, Long J, Han BG, Kubo M, Yamamoto K, Su MH, Miki T, Henderson BE, Song H, Tan A, He J, Ng DP, Cai Q, Tsunoda T, Tsai FJ, Iwai N, Chen GK, Shi J, Xu J, Sim X, Xiang YB, Maeda S, Ong RT, Li C, Nakamura Y, Aung T, Kamatani N, Liu JJ, Lu W, Yokota M, Seielstad M, Fann CS, Genetic Investigation of ANthropometric Traits (GIANT) Consortium, Wu JY, Lee JY, Hu FB, Tanaka T, Tai ES, Shu XO (2012) Meta-analysis identifies common variants associated with body mass index in East Asians. Nat Genet 44(3):307–311PubMedCentralPubMedGoogle Scholar
  194. Whitaker RC, Wright JA, Pepe MS, Seidel KD, Dietz WH (1997) Predicting obesity in young adulthood from childhood and parental obesity. N Engl J Med 337(13):869–873PubMedGoogle Scholar
  195. Widiker S, Karst S, Wagener A, Brockmann GA (2010) High-fat diet leads to a decreased methylation of the Mc4r gene in the obese BFMI and the lean B6 mouse lines. J Appl Genet 51:193–197PubMedGoogle Scholar
  196. Willer CJ, Speliotes EK, Loos RJ, Li S, Lindgren CM, Heid IM, Berndt SI, Elliott AL, Jackson AU, Lamina C, Lettre G, Lim N, Lyon HN, McCarroll SA, Papadakis K, Qi L, Randall JC, Roccasecca RM, Sanna S, Scheet P, Weedon MN, Wheeler E, Zhao JH, Jacobs LC, Prokopenko I, Soranzo N, Tanaka T, Timpson NJ, Almgren P, Bennett A, Bergman RN, Bingham SA, Bonnycastle LL, Brown M, Burtt NP, Chines P, Coin L, Collins FS, Connell JM, Cooper C, Smith GD, Dennison EM, Deodhar P, Elliott P, Erdos MR, Estrada K, Evans DM, Gianniny L, Gieger C, Gillson CJ, Guiducci C, Hackett R, Hadley D, Hall AS, Havulinna AS, Hebebrand J, Hofman A, Isomaa B, Jacobs KB, Johnson T, Jousilahti P, Jovanovic Z, Khaw KT, Kraft P, Kuokkanen M, Kuusisto J, Laitinen J, Lakatta EG, Luan J, Luben RN, Mangino M, McArdle WL, Meitinger T, Mulas A, Munroe PB, Narisu N, Ness AR, Northstone K, O’Rahilly S, Purmann C, Rees MG, Ridderstråle M, Ring SM, Rivadeneira F, Ruokonen A, Sandhu MS, Saramies J, Scott LJ, Scuteri A, Silander K, Sims MA, Song K, Stephens J, Stevens S, Stringham HM, Tung YC, Valle TT, Van Duijn CM, Vimaleswaran KS, Vollenweider P, Waeber G, Wallace C, Watanabe RM, Waterworth DM, Watkins N, Wellcome Trust Case Control Consortium, Witteman JC, Zeggini E, Zhai G, Zillikens MC, Altshuler D, Caulfield MJ, Chanock SJ, Farooqi IS, Ferrucci L, Guralnik JM, Hattersley AT, Hu FB, Jarvelin MR, Laakso M, Mooser V, Ong KK, Ouwehand WH, Salomaa V, Samani NJ, Spector TD, Tuomi T, Tuomilehto J, Uda M, Uitterlinden AG, Wareham NJ, Deloukas P, Frayling TM, Groop LC, Hayes RB, Hunter DJ, Mohlke KL, Peltonen L, Schlessinger D, Strachan DP, Wichmann HE, McCarthy MI, Boehnke M, Barroso I, Abecasis GR, Hirschhorn JN, Genetic Investigation of ANthropometric Traits Consortium (2009) Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet 41:25–34PubMedCentralPubMedGoogle Scholar
  197. Williams MD, Mitchell GM (2012) MicroRNAs in insulin resistance and obesity. Exp Diabetes Res 2012:484696PubMedCentralPubMedGoogle Scholar
  198. Wolff GL, Kodell RL, Moore SR, Cooney CA (1998) Maternal epigenetics and methyl supplements affect agouti gene expression in Avy/a mice. FASEB J 12:949–957PubMedGoogle Scholar
  199. Wu Q, Saunders RA, Szkudlarek-Mikho M, Serna Ide L, Chin KV (2010) The obesity-associated Fto gene is a transcriptional coactivator. Biochem Biophys Res Commun 401(3):390–395PubMedCentralPubMedGoogle Scholar
  200. Xi B, Chandak GR, Shen Y, Wang Q, Zhou D (2012) Association between common polymorphism near the MC4R gene and obesity risk: a systematic review and meta-analysis. PLoS ONE 7(9):e45731PubMedCentralPubMedGoogle Scholar
  201. Xia Q, Grant SF (2013) The genetics of human obesity. Ann N Y Acad Sci 1281:178–190PubMedCentralPubMedGoogle Scholar
  202. Xie H, Lim B, Lodish HF (2009) MicroRNAs induced during adipogenesis that accelerate fat cell development are downregulated in obesity. Diabetes 58:1050–1057PubMedCentralPubMedGoogle Scholar
  203. Xu X, Su S, Barnes VA, De Miguel C, Pollock J, Ownby D, Shi H, Zhu H, Snieder H, Wang X (2013) A genome-wide methylation study on obesity: differential variability and differential methylation. Epigenetics 8(5):522–533PubMedCentralPubMedGoogle Scholar
  204. Yang J, Manolio TA, Pasquale LR, Boerwinkle E, Caporaso N, Cunningham JM, de Andrade M, Feenstra B, Feingold E, Hayes MG, Hill WG, Landi MT, Alonso A, Lettre G, Lin P, Ling H, Lowe W, Mathias RA, Melbye M, Pugh E, Cornelis MC, Weir BS, Goddard ME, Visscher PM (2011) Genome partitioning of genetic variation for complex traits using common SNPs. Nat Genet 43(6):519–525PubMedCentralPubMedGoogle Scholar
  205. Yeo GS, Farooqi IS, Aminian S, Halsall DJ, Stanhope RG, O’Rahilly S (1998) A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nat Genet 20:111–112PubMedGoogle Scholar
  206. Zavattari P, Loche A, Pilia S, Ibba A, Moi L, Guzzetti C, Casini MR, Loche S (2011) rs9939609 in the FTO gene is associated with obesity but not with several biochemical parameters in Sardinian obese children. Ann Hum Genet 75:648–654PubMedGoogle Scholar
  207. Zhao J, Grant SF (2011) Genetics of childhood obesity. J Obes 2011:e845148Google Scholar
  208. Zhao J, Bradfield JP, Li M, Wang K, Zhang H, Kim CE, Annaiah K, Glessner JT, Thomas K, Garris M, Frackelton EC, Otieno FG, Shaner JL, Smith RM, Chiavacci RM, Berkowitz RI, Hakonarson H, Grant SF (2009) The role of obesity-associated loci identified in genome-wide association studies in the determination of pediatric BMI. Obesity (Silver Spring) 17(12):2254–2257Google Scholar
  209. Zhao J, Bradfield JP, Zhang H, Sleiman PM, Kim CE, Glessner JT, Deliard S, Thomas KA, Frackelton EC, Li M, Chiavacci RM, Berkowitz RI, Hakonarson H, Grant SF (2011) Role of BMI-associated loci identified in GWAS meta-analyses in the context of common childhood obesity in European Americans. Obesity (Silver Spring) 19:2436–2439Google Scholar
  210. Zhao J, Goldberg J, Vaccarino V (2013) Promoter methylation of serotonin transporter gene is associated with obesity measures: a monozygotic twin study. Int J Obes 37(1):140–145Google Scholar
  211. Zhu J, Loos RJ, Lu L, Zong G, Gan W, Ye X, Sun L, Li H, Lin X (2014) Associations of genetic risk score with obesity and related traits and the modifying effect of physical activity in a chinese han population. PLoS ONE 9(3):e91442PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • David Albuquerque
    • 1
  • Eric Stice
    • 2
  • Raquel Rodríguez-López
    • 3
  • Licíno Manco
    • 1
  • Clévio Nóbrega
    • 4
  1. 1.Department of Life Sciences, Research Centre for Anthropology and Health (CIAS)University of CoimbraCoimbraPortugal
  2. 2.Oregon Research InstituteEugeneUSA
  3. 3.Servicio de Análisis ClínicosConsorcio Hospital General de ValenciaValenciaSpain
  4. 4.Center for Neurosciences and Cell BiologyUniversity of CoimbraCoimbraPortugal

Personalised recommendations