Skip to main content

The Genetic Determinants of Common Obesity-Susceptibility

  • Chapter
  • First Online:
Adipose Tissue Biology

Abstract

Despite a relatively high heritability, the search for obesity-susceptibility genes has been challenging. While over the past 15 years, candidate gene studies and genome-wide linkage studies were able to identify only a handful of genetic variants convincingly associated with obesity-related traits, the genome-wide association approach has truly revolutionised gene discovery for many common diseases and traits, including obesity. In less than 4 years time, large-scale genome-wide association studies for body mass index, waist-to-hip ratio and extreme obesity have identified at least 50 obesity-susceptibility loci, most of which had not previously been linked to body weight regulation. Although the combined contribution of these genetic loci to the variation in obesity risk at the population level is small and their predictive value is low, it is anticipated that the recently identified loci will shed new light on the complex physiology that governs the regulation of energy balance and fat distribution. The expectation is that the genetic loci will point towards novel causal pathways and, subsequently, to the identification of therapeutic targets within these pathways. This new knowledge could eventually lead to the development of agents for more effective preventive and therapeutic interventions. While the rapid progress in gene discovery has raised hopes towards the development of genetic risk profiles to guide individual weight management, the current evidence suggests that the available genetic data is not sufficient for such personalised implementations.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abdel-Halim SM, Guenifi A, He B et al (1998) Mutations in the promoter of adenylyl cyclase (AC)-III gene, overexpression of AC-III mRNA, and enhanced cAMP generation in islets from the spontaneously diabetic GK rat model of type 2 diabetes. Diabetes 47:498–504

    PubMed  CAS  Google Scholar 

  • Adeyemo A, Chen G, Zhou J et al (2010) FTO genetic variation and association with obesity in West Africans and African Americans. Diabetes 59:1549–1554

    PubMed  CAS  Google Scholar 

  • Ahmad T, Chasman DI, Mora S et al (2010) The fat-mass and obesity-associated (FTO) gene, physical activity, and risk of incident cardiovascular events in white women. Am Heart J 160:1163–1169

    PubMed  Google Scholar 

  • Al-Attar SA, Pollex RL, Ban MR et al (2008) Association between the FTO rs9939609 polymorphism and the metabolic syndrome in a non-Caucasian multi-ethnic sample. Cardiovasc Diabetol 7:5

    PubMed  Google Scholar 

  • Allison DB, Faith J, Nathan JS (1996) Risch’s lambda values for human obesity. Int J Obes Relat Metab Disord 20:990–999

    PubMed  CAS  Google Scholar 

  • Allison DB, Heo M, Faith MS et al (1998) Meta-analysis of the association of the Trp64Arg polymorphism in the beta3 adrenergic receptor with body mass index. Int J Obes Relat Metab Disord 22:559–566

    PubMed  CAS  Google Scholar 

  • Andersen G, Wegner L, Yanagisawa K et al (2005) Evidence of an association between genetic variation of the coactivator PGC-1{beta} and obesity. J Med Genet 42:402–407

    PubMed  CAS  Google Scholar 

  • Andersson EA, Holst B, Sparso T et al (2010) The MTNR1B G24E variant associates with BMI and fasting plasma glucose in the general population in studies of 22,142 Europeans. Diabetes 59:1539–1548

    PubMed  CAS  Google Scholar 

  • Andreasen C, Mogensen M, Borch-Johnsen K et al (2008a) Lack of association between PKLR rs3020781 and NOS1AP rs7538490 and type 2 diabetes, overweight, obesity and related metabolic phenotypes in a Danish large-scale study: Case-control studies and analyses of quantitative traits. BMC Med Genet 9:118

    PubMed  Google Scholar 

  • Andreasen CH, Stender-Petersen KL, Mogensen MS et al (2008b) Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation. Diabetes 57:264–268

    Google Scholar 

  • Bachmann-Gagescu R, Mefford HC, Cowan C et al (2010) Recurrent 200-kb deletions of 16p11.2 that include the SH2B1 gene are associated with developmental delay and obesity. Gene Med 12:641–647

    Google Scholar 

  • Baker K, Beales PL (2009) Making sense of cilia in disease: The human ciliopathies. Am J Med Genet C: Semin Med Genet 151C:281–295

    CAS  Google Scholar 

  • Been LF, Nath SK, Ralhan SK et al (2009) Replication of association between a common variant near melanocortin-4 receptor gene and obesity-related traits in Asian sikhs. Obesity Res 18:425–429

    Google Scholar 

  • Begin-Heick N (1994) Liver beta-adrenergic receptors, G proteins, and adenylyl cyclase activity in obesity-diabetes syndromes. Am J Physiol – Cell Physiol 266:C1664–C1672

    CAS  Google Scholar 

  • Benzinou M, Creemers JW, Choquet H et al (2008) Common nonsynonymous variants in PCSK1 confer risk of obesity. Nat Genet 40:943–945

    PubMed  CAS  Google Scholar 

  • Berentzen T, Kring SII, Holst C et al (2008) Lack of association of fatness-related FTO gene variants with energy expenditure or physical activity. J Clin Endocrinol Metab 93:2904–2908

    PubMed  CAS  Google Scholar 

  • Bochukova EG, Huang N, Keogh J et al (2010) Large, rare chromosomal deletions associated with severe early-onset obesity. Nature 463:666–670

    PubMed  CAS  Google Scholar 

  • Boesgaard TW, Gjesing AP, Grarup N et al (2009) Variant near ADAMTS9 known to associate with Type 2 diabetes is related to insulin resistance in offspring of Type 2 diabetes patientsΓÇöEUGENE2 study. PLoS ONE 4:e7236

    PubMed  Google Scholar 

  • Bollepalli S, Dolan LM, Deka R et al (2010) Association of FTO gene variants with adiposity in African-American adolescents. Obesity Res 18:1959–1963

    CAS  Google Scholar 

  • Bouatia-Naji N, Bonnefond A, Cavalcanti-Proenca C et al (2009) A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk. Nat Genet 41:89–94

    PubMed  CAS  Google Scholar 

  • Bouchard C, Tremblay A, Despres JP et al (1990) The response to long-term overfeeding in identical twins. N Engl J Med 322:1477–1482

    PubMed  CAS  Google Scholar 

  • Bouchard C, Tremblay A, Despres JP et al (1994) The response to exercise with constant energy intake in identical twins. Obes Res 2:400–410

    PubMed  CAS  Google Scholar 

  • Bressler J, Kao WHL, Pankow JS et al (2010) Risk of Type 2 diabetes and obesity is differentially associated with variation in FTO in Whites and African-Americans in the ARIC study. PLoS ONE 5:e10521

    PubMed  Google Scholar 

  • Burgdorf KS, Sandholt CH, Sparso T et al (2010) Studies of association between LPIN1 variants and common metabolic phenotypes among 17 538 Danes. Eur J Endocrinol 163:81–87

    PubMed  CAS  Google Scholar 

  • Campbell CD, Lyon HN, Nemesh J et al (2007) Association studies of BMI and Type 2 diabetes in the neuropeptide Y pathway: A possible role for NPY2R as a candidate gene for Type 2 diabetes in men. Diabetes 56:1460–1467

    PubMed  CAS  Google Scholar 

  • Cauchi S, Stutzmann F, Cavalcanti-Proena C et al (2009) Combined effects of MC4R and FTO common genetic variants on obesity in European general populations. J Mol Med 87:537–546

    PubMed  CAS  Google Scholar 

  • Cecil JE, Tavendale R, Watt P et al (2008) An obesity-associated FTO gene variant and increased energy intake in children. N Engl J Med 359:2558–2566

    PubMed  CAS  Google Scholar 

  • Cha SW, Choi SM, Kim KS et al (2008) Replication of genetic effects of FTO polymorphisms on BMI in a Korean population. Obesity (Silver Spring) 16:2187–2189

    CAS  Google Scholar 

  • Chambers JC, Elliott P, Zabaneh D et al (2008) Common genetic variation near MC4R is associated with waist circumference and insulin resistance. Nat Genet 40:716–718

    PubMed  CAS  Google Scholar 

  • Chang TY, Reid PC, Shugii S et al (2005) Niemann-pick Type C disease and intracellular cholesterol trafficking. J Biol Chem 3:20917–20920

    Google Scholar 

  • Chang YC, Liu PH, Lee WJ et al (2008) Common variation in the fat mass and obesity-associated (FTO) gene confers risk of obesity and modulates BMI in the Chinese population. Diabetes 57:2245–2252

    PubMed  CAS  Google Scholar 

  • Chen ZY, Patel PD, Sant G et al (2004) Variant Brain-Derived Neurotrophic Factor (BDNF) (Met66) alters the intracellular trafficking and activity-dependent secretion of wild-type BDNF in neurosecretory cells and cortical neurons. J Neurosci 24:4401–4411

    PubMed  CAS  Google Scholar 

  • Cheung CYY, Tso AWK, Cheung BMY et al (2010) Obesity-susceptibility genetic variants identified from recent genome-wide association studies: Implications in a Chinese population. J Clin Endocrinol Metab 95:1395–1403

    PubMed  CAS  Google Scholar 

  • Cho YS, Go MJ, Kim YJ et al (2009) A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits. Nat Genet 41:527–534

    PubMed  CAS  Google Scholar 

  • Church C, Lee S, Bagg EAL et al (2009) A mouse model for the metabolic effects of the human fat mass and obesity associated FTO gene. PLoS Genet 5:e1000599

    PubMed  Google Scholar 

  • Church C, Moir L, McMurray F et al (2010) Overexpression of FTO leads to increased food intake and results in obesity. Nat Genet 42:1086–1092

    PubMed  CAS  Google Scholar 

  • Claustrat B, Brun J, Chazot G (2005) The basic physiology and pathophysiology of melatonin. Sleep Med Rev 9:11–24

    PubMed  Google Scholar 

  • Clement K, Vaisse C, Manning BS et al (1995) Genetic variation in the β3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity. N Engl J Med 333:352–354

    PubMed  CAS  Google Scholar 

  • Conrad DF, Pinto D, Redon R et al (2010) Origins and functional impact of copy number variation in the human genome. Nature 464:704–712

    PubMed  CAS  Google Scholar 

  • Contopoulos-Ioannidis DG, Alexiou GA, Gouvias TC et al (2008) Life cycle of translational research for medical interventions. Science 321:1298–1299

    PubMed  CAS  Google Scholar 

  • Cooney GJ, Lyons RJ, Crew AJ et al (2004) Improved glucose homeostasis and enhanced insulin signalling in Grb14-deficient mice. EMBO J 23:582–593

    PubMed  CAS  Google Scholar 

  • Croteau-Chonka DC, Marvelle AF, Lange EM et al. (2011) Genome-wide association study of anthropometric traits and evidence of interactions with age and study year in Filipino women. Obesity 19:1019–1027

    Google Scholar 

  • Cunningham SA, Ruben JD, Venkat Narayan KM (2008) Health of foreign-born people in the United States: A review. Health & Place 14:623–635

    Google Scholar 

  • de Bakker PIW, Ferreira MAR, Jia X et al (2008) Practical aspects of imputation-driven meta-analysis of genome-wide association studies. Hum Mol Genet 17:R122–R128

    PubMed  Google Scholar 

  • De Moor MHM, Liu YJ, Boomsma DI et al. (2009) Genome-wide association study of exercise behavior in Dutch and American adults. Med Sci Sports Exerc 41:897–905

    Google Scholar 

  • den Hoed M, Ekelund U, Brage S et al (2010) Genetic susceptibility to obesity and related traits in childhood and adolescence. Diabetes 59:2980–2988

    Google Scholar 

  • Do R, Bailey SD, Desbiens K et al (2008) Genetic variants of FTO influence adiposity, insulin sensitivity, leptin levels, and resting metabolic rate in the Quebec family study. Diabetes 57:1147–1150

    PubMed  CAS  Google Scholar 

  • Egan MF, Kojima M, Callicott JH et al (2003) The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 112:257–269

    PubMed  CAS  Google Scholar 

  • Enattah NS, Sahi T, Savilahti E et al (2002) Identification of a variant associated with adult-type hypolactasia. Nat Genet 30:233–237

    PubMed  CAS  Google Scholar 

  • Enocksson S, Shimizu M, Lonnqvist F et al (1995) Demonstration of an in vivo functional beta 3-adrenoceptor in man. J Clin Invest 95(5):2239–2245

    PubMed  CAS  Google Scholar 

  • Fan W, Boston BA, Kesterson RA et al (1997) Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature 385:165–168

    PubMed  CAS  Google Scholar 

  • Fang H, Li Y, Du S et al (2010) Variant rs9939609 in the FTO gene is associated with body mass index among Chinese children. BMC Med Genet 11:136

    PubMed  Google Scholar 

  • Farooqi IS, O’Rahilly S (2008) Mutations in ligands and receptors of the leptin-melanocortin pathway that lead to obesity. Nat Clin Pract End Met 4:569–577

    CAS  Google Scholar 

  • Farooqi IS, Keogh JM, Yeo GSH et al (2003) Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med 348:1085–1095

    PubMed  CAS  Google Scholar 

  • Farooqi IS, Volders K, Stanhope R et al (2007) Hyperphagia and early-onset obesity due to a novel homozygous missense mutation in prohormone convertase 1/3. J Clin Endocrinol Metab 92:3369–3373

    PubMed  CAS  Google Scholar 

  • Fawcett KA, Grimsey N, Loos RJ et al (2008) Evaluating the role of LPIN1 variation in insulin resistance, body weight, and human lipodystrophy in U.K. populations. Diabetes 57:2527–2533

    PubMed  CAS  Google Scholar 

  • Fischer J, Koch L, Emmerling C et al (2009) Inactivation of the Fto gene protects from obesity. Nature 458:894–898

    PubMed  CAS  Google Scholar 

  • Flegal KM, Caroll MD, Kuczmarski RJ et al (1998) Overweight and obesity in the United States: Prevalence and trends, 1960–1994. Int J Obes Relat Metab Disord 22:39–47

    PubMed  CAS  Google Scholar 

  • Flegal KM, Carroll MD, Ogden CL et al (2010) Prevalence and trends in obesity among US adults, 1999–2008. JAMA: J Am Med Assoc 303:235–241

    CAS  Google Scholar 

  • Fox EA, Byerly MS (2004) A mechanism underlying mature-onset obesity: Evidence from the hyperphagic phenotype of brain-derived neurotrophic factor mutants. Am J Physiol Regul Integr Comp Physiol 286:R994–1004

    PubMed  CAS  Google Scholar 

  • Frayling TM, Timpson NJ, Weedon MN et al (2007) A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316:889–894

    PubMed  CAS  Google Scholar 

  • Fredriksson R, Hagglund M, Olszewski PK et al (2008) The obesity gene, FTO, is of ancient origin, upregulated during food deprivation and expressed in neurons of feeding-related nuclei of the brain. Endocrinology 149:2062–2071

    PubMed  CAS  Google Scholar 

  • Fujisawa T, Ikegami H, Kawaguchi Y et al (1998) Meta-analysis of the association of Trp64Arg polymorphism of β3-adrenergic receptor gene with body mass index. J Clin Endocrinol Metab 83:2441

    PubMed  CAS  Google Scholar 

  • Garcia de la Torre N, Rubio MA, Bordiu E et al (2008) Effects of weight loss after bariatric surgery for morbid obesity on vascular endothelial growth factor-A, adipocytokines, and insulin. J Clin Endocrinol Metab 93:4276–4281

    PubMed  CAS  Google Scholar 

  • Geller F, Reichwald K, Dempfle A et al (2004) Melanocortin 4 receptor gene variant I103 is negatively associated with obesity. Am J Hum Genet 74:572–581

    PubMed  CAS  Google Scholar 

  • Gerken T, Girard CA, Tung YCL et al (2007) The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 318:1469–1472

    PubMed  CAS  Google Scholar 

  • Gjesing AP, Andersen G, Albrechtsen A et al (2007a) Studies of associations between the Arg389Gly polymorphism of the beta1-adrenergic receptor gene (ADRB1) and hypertension and obesity in 7677 Danish white subjects. Diabetic Med 24:392–397

    PubMed  CAS  Google Scholar 

  • Gjesing AP, Andersen G, Burgdorf KS et al (2007b) Studies of the associations between functional beta2-adrenergic receptor variants and obesity, hypertension and type 2 diabetes in 7,808 white subjects. Diabetologia 50:563–568

    PubMed  CAS  Google Scholar 

  • Gjesing AP, Andersen G, Borch-Johnsen K et al (2008) Association of the [beta]3-adrenergic receptor Trp64Arg polymorphism with common metabolic traits: Studies of 7605 middle-aged white people. Mol Genet Metab 94:90–97

    PubMed  CAS  Google Scholar 

  • Gjesing AP, Larsen LH, Torekov SS et al (2010) Family and population-based studies of variation within the Ghrelin receptor locus in relation to measures of obesity. PLoS ONE 5:e10084

    PubMed  Google Scholar 

  • Goossens GH, Petersen L, Blaak EE et al (2009) Several obesity- and nutrient-related gene polymorphisms but not FTO and UCP variants modulate postabsorptive resting energy expenditure and fat-induced thermogenesis in obese individuals: The NUGENOB study. Int J Obes 33:669–679

    CAS  Google Scholar 

  • Grant SFA, Li M, Bradfield JP et al (2008) Association analysis of the FTO gene with obesity in children of Caucasian and African ancestry reveals a common tagging SNP. PLoS ONE 3:e1746

    PubMed  Google Scholar 

  • Grant SFA, Bradfield JP, Zhang H et al (2009) Investigation of the locus near MC4R with childhood obesity in Americans of European and African ancestry. Obesity Res 17:1461–1465

    Google Scholar 

  • Grarup N, Urhammer SA, Ek J et al (2006) Studies of the relationship between the ENPP1 K121Q polymorphism and type 2 diabetes, insulin resistance and obesity in 7,333 Danish white subjects. Diabetologia 49:2097–2104

    PubMed  CAS  Google Scholar 

  • Grarup N, Albrechtsen A, Ek J et al (2007a) Variation in the peroxisome proliferator-activated receptor delta gene in relation to common metabolic traits in 7,495 middle-aged white people. Diabetologia 50:1201–1208

    PubMed  CAS  Google Scholar 

  • Grarup N, Andersen MK, Andreasen CH et al (2007b) Studies of the common DIO2 Thr92Ala polymorphism and metabolic phenotypes in 7342 Danish White subjects. J Clin Endocrinol Metab 92:363–366

    PubMed  CAS  Google Scholar 

  • Gray J, Yeo GSH, Cox JJ et al (2006) Hyperphagia, severe obesity, impaired cognitive function, and hyperactivity associated with functional loss of one copy of the Brain-Derived Neurotrophic Factor (BDNF) gene. Diabetes 55:3366–3371

    PubMed  CAS  Google Scholar 

  • Hainer V, Stunkard AJ, Kunesova M et al (2000) Intrapair resemblance in very low calorie diet-induced weight loss in female obese identical twins. Int J Obes Relat Metab Disord 24:1051–1057

    PubMed  CAS  Google Scholar 

  • Hakanen M, Raitakari OT, Lehtimaki T et al (2009) FTO genotype is associated with body mass index after the age of 7 years but not with energy intake or leisure-time physical activity. J Clin Endocrinol Metab 94:1281–1287

    PubMed  CAS  Google Scholar 

  • Hamid YH, Urhammer SA, Glumer C et al (2005) The common T60N polymorphism of the lymphotoxin-alpha gene is associated with type 2 diabetes and other phenotypes of the metabolic syndrome. Diabetologia 48:445–451

    PubMed  CAS  Google Scholar 

  • Han JC, Liu QR, Jones M et al (2008) Brain-derived neurotrophic factor and obesity in the WAGR syndrome. N Engl J Med 359:918–927

    PubMed  CAS  Google Scholar 

  • Han X, Luo Y, Ren Q et al (2010) Implication of genetic variants near SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, FTO, TCF2, KCNQ1, and WFS1 in Type 2 diabetes in a Chinese population. BMC Med Genet 11:81

    PubMed  Google Scholar 

  • Hardy R, Wills AK, Wong A et al (2010) Life course variations in the associations between FTO and MC4R gene variants and body size. Hum Mol Genet 19:545–552

    PubMed  CAS  Google Scholar 

  • Hassanein MT, Lyon HN, Nguyen TT et al (2010) Fine mapping of the association with obesity at the FTO locus in African-derived populations. Hum Mol Genet 19:2907–2916

    PubMed  CAS  Google Scholar 

  • Haupt A, Thamer C, Machann J et al (2008) Impact of variation in the FTO gene on whole body fat distribution, ectopic fat, and weight loss. Obesity Res 16:1969–1972

    Google Scholar 

  • Haupt A, Thamer C, Staiger H et al (2009) Variation in the FTO Gene Influences Food Intake but not Energy Expenditure. Exp Clin Endocrinol Diabetes 117:194–197

    PubMed  CAS  Google Scholar 

  • Haworth CMA, Carnell S, Meaburn EL et al (2008) Increasing heritability of BMI and stronger associations with the FTO gene over childhood. Obesity Res 16:2663–2668

    Google Scholar 

  • Heard-Costa NL, Zillikens MC, Monda KL et al (2009) NRXN3 is a novel locus for waist circumference: A genome-wide association study from the CHARGE consortium. PLoS Genet 5:e1000539

    PubMed  Google Scholar 

  • Heid IM, Vollmert C, Hinney A et al (2005) Association of the 103I MC4R allele with decreased body mass in 7937 participants of two population based surveys. J Med Genet 42:e21

    PubMed  CAS  Google Scholar 

  • Heid IM, Jackson AU, Randall JC et al (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 42:949–960

    PubMed  CAS  Google Scholar 

  • Hennig B, Fulford A, Sirugo G et al (2009) FTO gene variation and measures of body mass in an African population. BMC Med Genet 10:21

    PubMed  Google Scholar 

  • Heo M, Leibel R, Fontaine KR et al (2002) A meta-analytic investigation of linkage and association of common leptin receptor (LEPR) polymorphisms with body mass index and waist circumference. Int J Obes Relat Metab Disord 26:640–646

    PubMed  CAS  Google Scholar 

  • Heude B, Ong KK, Luben R et al (2007) Study of association between common variation in the insulin-like growth factor 2 gene and indices of obesity and body size in middle-aged men and women. J Clin Endocrinol Metab 92:2734–2738

    PubMed  CAS  Google Scholar 

  • Hindorff LA, Junkins HA, Manolio TA (2010) NHGRI catalog of published genome-wide association studies (http://www.genome.gov/gwastudies).

  • Hinney A, Nguyen TT, Scherag A et al (2007) Genome Wide Association (GWA) study for early onset extreme obesity supports the role of fat mass and obesity associated gene (FTO) Variants. PLoS ONE 2:e1361

    PubMed  Google Scholar 

  • Hotta K, Nakata Y, Matsuo T et al (2008) Variations in the FTO gene are associated with severe obesity in the Japanese. J Hum Genet 53:546–553

    PubMed  CAS  Google Scholar 

  • Hotta K, Nakamura M, Nakamura T et al (2009) Association between obesity and polymorphisms in SEC16B, TMEM18, GNPDA2, BDNF, FAIM2 and MC4R in a Japanese population. J Hum Genet 54:727–731

    PubMed  CAS  Google Scholar 

  • Hotta K, Nakamura M, Nakamura T et al (2010) Polymorphisms in NRXN3, TFAP2B, MSRA, LYPLAL1, FTO and MC4R and their effect on visceral fat area in the Japanese population. J Hum Genet 55:738–742

    PubMed  CAS  Google Scholar 

  • Human Genome Sequencing Consortium (2004) Finishing the euchromatic sequence of the human genome. Nature 431:931–945

    Google Scholar 

  • Huszar D, Lynch CA, Fairchild-Huntress V et al (1997) Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88:131–141

    PubMed  CAS  Google Scholar 

  • Huth C, Illig T, Herder C et al (2009) Joint analysis of individual participants data from 17 studies on the association of the IL6 variant -174 G  >  C with circulating glucose levels, interleukin-6 levels, and body mass index. Ann Med 41:128–138

    PubMed  CAS  Google Scholar 

  • International Association for the Study of Obesity. http://www.iotf.org/. http://www.iotf.org/. 2010.

  • Jackson RS, Creemers JWM, Ohagi S et al (1997) Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat Genet 16:303–306

    PubMed  CAS  Google Scholar 

  • Jackson RS, Creemers JW, Farooqi IS et al (2003) Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency. J Clin Invest 112:1550–1560

    PubMed  CAS  Google Scholar 

  • Jaddoe V, Bakker R, van Duijn C et al (2007) The Generation R Study Biobank: a resource for epidemiological studies in children and their parents. Eur J Epidemiol 22:917–923

    PubMed  Google Scholar 

  • Jalba MS, Rhoads GG, Demissie K (2008) Association of Codon 16 and Codon 27 β2-adrenergic receptor gene polymorphisms with obesity: A meta-analysis. Obesity Res 16:2096–2106

    CAS  Google Scholar 

  • Jensen D, Andreasen C, Andersen M et al (2007) The functional Pro129Thr variant of the FAAH gene is not associated with various fat accumulation phenotypes in a population-based cohort of 5,801 whites. J Mol Med 85:445–449

    PubMed  CAS  Google Scholar 

  • Jonsson A, Renstrom F, Lyssenko V et al (2009) Assessing the effect of interaction between an FTO variant (rs9939609) and physical activity on obesity in 15,925 Swedish and 2,511 Finnish adults. Diabetologia 52:1334–1338

    PubMed  CAS  Google Scholar 

  • Kang SJ, Chiang CWK, Palmer CD et al (2010) Genome-wide association of anthropometric traits in African- and African-derived populations. Hum Mol Genet 19:2725–2738

    PubMed  CAS  Google Scholar 

  • Katzmarzyk PT, Perusse L, Rao DC et al (1999) Familial risk of obesity and central adipose tissue distribution in the general Canadian population. Am J Epidemiol 149:933–942

    PubMed  CAS  Google Scholar 

  • Kernie SG, Liebl DJ, Parada LF (2000) BDNF regulates eating behavior and locomotor activity in mice. EMBO J 19:1290–1300

    PubMed  CAS  Google Scholar 

  • Kettunen J, Silander K, Saarela O et al (2010) European lactase persistence genotype shows evidence of association with increase in body mass index. Hum Mol Genet 19:1129–1136

    PubMed  CAS  Google Scholar 

  • Kiehl TR, Nechiporuk A, Figueroa KP et al (2006) Generation and characterization of Sca2 (ataxin-2) knockout mice. Biochemical Biophysical Res Commun 339:17–24

    CAS  Google Scholar 

  • Kilpelainen TO, Bingham SA, Khaw KT et al (2009) Association of variants in the PCSK1 gene with obesity in the EPIC-Norfolk study. Hum Mol Genet 18:3496–3501

    PubMed  CAS  Google Scholar 

  • Kilpelainen TO, den Hoed M, Ong KK et al (2011) Obesity-susceptibility loci have limited influence on birth weight: a meta-analysis of up to 28,219 individuals. Am J Clin Nutr 93(4):851–860

    Google Scholar 

  • Kimura K, Sasaki N, Asano A et al (2000) Mutated human beta3-adrenergic receptor (Trp64Arg) lowers the response to beta3-adrenergic agonists in transfected 3 T3-L1 preadipocytes. Horm Metab Res 32:91–96

    PubMed  CAS  Google Scholar 

  • Kleyn PW, Fan W, Kovats SG et al (1996) Identification and characterization of the mouse obesity gene tubby: A member of a novel gene family. Cell 85:281–290

    PubMed  CAS  Google Scholar 

  • Knowler WC, Pettitt DJ, Saad MF et al (1991) Obesity in the Pima Indians: Its magnitude and relationship with diabetes. Am J Clin Nutr 53:1543S–1551S

    PubMed  CAS  Google Scholar 

  • Korkeila M, Kaprio J, Rissanen A et al (1991) Effects of gender and age on the heritability of body mass index. Int J Obes 15:647–654

    PubMed  CAS  Google Scholar 

  • Kurokawa N, Nakai K, Kameo S et al (2001) Association of BMI with the b3-adrenergic receptor gene polymorphism in Japanese: Meta-analysis. Obes Res 9:741

    PubMed  CAS  Google Scholar 

  • Kurokawa N, Young EH, Oka Y et al (2008) The ADRB3 Trp64Arg variant and BMI: A meta-analysis of 44 833 individuals. Int J Obes (Lond) 32:1240–1249

    CAS  Google Scholar 

  • Lafontan M, Berlan M (1993) Fat cell adrenergic receptors and the control of white and brown fat cell function. J Lipid Res 34:1057–1091

    PubMed  CAS  Google Scholar 

  • Lajunen HR, Kaprio J, Keski-Rahkonen A et al (2009) Genetic and environmental effects on body mass index during adolescence: A prospective study among Finnish twins. Int J Obes 33:559–567

    Google Scholar 

  • Larsen LH, Rose CS, Sparso T et al (2007) Genetic analysis of the estrogen-related receptor [alpha] and studies of association with obesity and type 2 diabetes. Int J Obes 31:365–370

    Google Scholar 

  • Lastres-Becker I, Brodesser S, Lutjohann D et al (2008) Insulin receptor and lipid metabolism pathology in ataxin-2 knock-out mice. Hum Mol Genet 17:1465–1481

    PubMed  CAS  Google Scholar 

  • Lee JH, Reed DR, Price RA (1997) Familial risk ratios for extreme obesity: Implications for mapping human obesity genes. Int J Obes Relat Metab Disord 21:935–940

    PubMed  CAS  Google Scholar 

  • Li S, Zhao JH, Luan J et al (2010a) Physical activity attenuates the genetic predisposition to obesity in 20,000 men and women from EPIC-Norfolk prospective population Study. PLoS Med 7:e1000332

    Google Scholar 

  • Li X, Song F, Jiang H et al (2010b) A genetic variation in the fat mass- and obesity-associated gene is associated with obesity and newly diagnosed type 2 diabetes in a Chinese population. Diabetes Metab Res Rev 26:128–132

    PubMed  CAS  Google Scholar 

  • Liem ET, Vonk JM, Sauer PJ et al (2010) Influence of common variants near INSIG2, in FTO, and near MC4R genes on overweight and the metabolic profile in adolescence: The TRAILS (TRacking Adolescents’ Individual Lives Survey) study. Am J Clin Nutr 91:321–328

    PubMed  CAS  Google Scholar 

  • Lindgren CM, Heid IM, Randall JC et al (2009) Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution. PLoS Genet 5:e1000508

    PubMed  Google Scholar 

  • Liu G, Zhu H, Lagou V et al (2010a) Common variants near melanocortin 4 receptor are associated with general and visceral adiposity in European- and African-American youth. J Pediat 156:598–605

    PubMed  CAS  Google Scholar 

  • Liu G, Zhu H, Lagou V et al (2010b) FTO variant rs9939609 is associated with body mass index and waist circumference, but not with energy intake or physical activity in European- and African-American youth. BMC Med Genet 11:57

    PubMed  Google Scholar 

  • Liu Y, Liu Z, Song Y et al (2010c) Meta-analysis added power to identify variants in FTO associated with Type 2 diabetes and obesity in the Asian population. Obesity Res 18:1619–1624

    CAS  Google Scholar 

  • Loos RJ, Lindgren CM, Li S et al (2008) Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat Genet 40:768–775

    PubMed  CAS  Google Scholar 

  • Lopez-Bermejo A, Petry CJ, Diaz M et al (2008) The association between the FTO gene and fat mass in humans develops by the postnatal age of two weeks. J Clin Endocrinol Metab 93:1501–1505

    PubMed  CAS  Google Scholar 

  • Luan JA, Wong MY, Day NE et al (2001) Sample size determination for studies of gene-­environment interaction. Int J Epidemiol 30:1035–1040

    PubMed  CAS  Google Scholar 

  • Lyon HN, Florez JC, Bersaglieri T et al (2006) Common variants in the ENPP1 gene are not reproducibly associated with diabetes or obesity. Diabetes 55:3180–3184

    PubMed  CAS  Google Scholar 

  • Lyssenko V, Nagorny CLF, Erdos MR et al (2009) Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion. Nat Genet 41:82–88

    PubMed  CAS  Google Scholar 

  • Ma L, Hanson RL, Traurig MT et al (2010) Evaluation of A2BP1 as an obesity gene. Diabetes 59:2837–2845

    PubMed  CAS  Google Scholar 

  • Maes HH, Neale MC, Eaves LJ (1997) Genetic and environmental factors in relative body weight and human obesity. Behav Genet 27:325–351

    PubMed  CAS  Google Scholar 

  • Manolio TA, Collins FS, Cox NJ et al (2009) Finding the missing heritability of complex diseases. Nature 461:747–753

    PubMed  CAS  Google Scholar 

  • McCarthy MI, Abecasis GR, Cardon LR et al (2008) Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat Rev Genet 9:356–369

    PubMed  CAS  Google Scholar 

  • Meyre D, Bouatia-Naji N, Tounian A et al (2005) Variants of ENPP1 are associated with childhood and adult obesity and increase the risk of glucose intolerance and type 2 diabetes. Nat Genet 37:863–867

    PubMed  CAS  Google Scholar 

  • Meyre D, Bouatia-Naji N, Vatin V et al (2007) ENPP1 K121Q polymorphism and obesity, hyperglycaemia and type 2 diabetes in the prospective DESIR Study. Diabetologia 50:2090–2096

    PubMed  CAS  Google Scholar 

  • Meyre D, Delplanque J, Chevre JC et al (2009) Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations. Nat Genet 41:157–159

    PubMed  CAS  Google Scholar 

  • Miot A, Maimaitiming S, Emery N et al (2010) Genetic variability at the six transmembrane protein of prostate 2 locus and the metabolic syndrome: The Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) study. J Clin Endocrinol Metab 95:2942–2947

    PubMed  CAS  Google Scholar 

  • Miyawaki K, Yamada Y, Ban N et al (2002) Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nat Med 8:738–742

    PubMed  CAS  Google Scholar 

  • Ng MC, Park KS, Oh B et al (2008) Implication of genetic variants near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in type 2 diabetes and obesity in 6,719 Asians. Diabetes 57:2226–2233

    PubMed  CAS  Google Scholar 

  • Ng MCY, Tam CHT, So WY et al (2010) Implication of genetic variants near NEGR1, SEC16B, TMEM18, ETV5/DGKG, GNPDA2, LIN7C/BDNF, MTCH2, BCDIN3D/FAIM2, SH2B1, FTO, MC4R, and KCTD15 with obesity and Type 2 diabetes in 7705 Chinese. J Clin Endocrinol Metab 95:2418–2425

    PubMed  CAS  Google Scholar 

  • Nishimura S, Manabe I, Nagasaki M et al (2007) Adipogenesis in obesity requires close interplay between differentiating adipocytes, stromal cells, and blood vessels. Diabetes 56:1517–1526

    PubMed  CAS  Google Scholar 

  • Norman RA, Thompson DB, Foroud T et al (1997) Genomewide search for genes influencing percent body fat in Pima Indians: suggestive linkage at chromosome 11q21-q22. Pima Diabetes Gene Group Am J Hum Genet 60:166–173

    CAS  Google Scholar 

  • O’Rahilly S (2009) Human genetics illuminates the paths to metabolic disease. Nature 462:307–314

    PubMed  Google Scholar 

  • Omori S, Tanaka Y, Takahashi A et al (2008) Association of CDKAL1, IGF2BP2, CDKN2A/B, HHEX, SLC30A8, and KCNJ11 with susceptibility to type 2 diabetes in a Japanese population. Diabetes 57:791–795

    PubMed  CAS  Google Scholar 

  • Pietri-Rouxel F (1997) St John Manning B, Gros J et al. The biochemical effect of the naturally occurring Trp64–  >  Arg mutation on human beta3-adrenoceptor activity. Eur J Biochem 247(3):1174–1179

    PubMed  CAS  Google Scholar 

  • Pischon T, Boeing H, Hoffmann K et al (2008) General and abdominal adiposity and risk of death in Europe. N Engl J Med 359:2105–2120

    PubMed  CAS  Google Scholar 

  • Popkin BM (2008) The world is fat – the fads, trends, policies, and products that are fattening the human race. Avery-Penguin Group, New York

    Google Scholar 

  • Prokopenko I, Langenberg C, Florez JC et al (2009) Variants in MTNR1B influence fasting glucose levels. Nat Genet 41:77–81

    PubMed  CAS  Google Scholar 

  • Qi L, Zhang C, van Dam RM et al (2007) Interleukin-6 genetic variability and adiposity: Associations in two prospective cohorts and systematic review in 26,944 individuals. J Clin Endocrinol Metab 92:3618–3625

    PubMed  CAS  Google Scholar 

  • Rampersaud E, Mitchell BD, Pollin TI et al (2008) Physical activity and the association of common FTO gene variants with body mass index and obesity. Arch Intern Med 168:1791–1797

    PubMed  Google Scholar 

  • Rankinen T, Zuberi A, Chagnon YC et al (2006) The human obesity gene map: The 2005 update. Obes Res 14:529–644

    Google Scholar 

  • Ravussin E, Valencia ME, Esparza J et al (1994) Effects of a traditional lifestyle on obesity in Pima Indians. Diabetes Care 17:1067–1074

    PubMed  CAS  Google Scholar 

  • Ren D, Zhou Y, Morris D et al (2007) Neuronal SH2B1 is essential for controlling energy and glucose homeostasis. J Clin Invest 117:397–406

    PubMed  CAS  Google Scholar 

  • Ridker PM, Pare G, Parker AN et al (2009) Polymorphism in the CETP gene region, HDL cholesterol, and risk of future myocardial infarction/clinical perspective. Circ: Cardiovasc Genet 2:26–33

    CAS  Google Scholar 

  • Rios M, Fan G, Fekete C et al (2001) Conditional deletion of brain-derived neurotrophic factor in the postnatal brain leads to obesity and hyperactivity. Mol Endocrinol 15:1748–1757

    PubMed  CAS  Google Scholar 

  • Rzehak P, Scherag A, Grallert H et al (2010) Associations between BMI and the FTO gene are age dependent: Results from the GINI and LISA birth cohort studies up to age 6 years. Obesity Facts 3:180

    Google Scholar 

  • Sanchez-Pulido L, Andrade-Navarro MA (2007) The FTO (fat mass and obesity associated) gene codes for a novel member of the non-heme dioxygenase superfamily. BMC Biochemistry 8:23

    PubMed  Google Scholar 

  • Sanghera D, Ortega L, Han S et al (2008) Impact of nine common type 2 diabetes risk polymorphisms in Asian Indian Sikhs: PPARG2 (Pro12Ala), IGF2BP2, TCF7L2 and FTO variants confer a significant risk. BMC Medical Genet 9:59

    Google Scholar 

  • Saunders CL, Chiodini BD, Sham P et al (2007) Meta-analysis of genome-wide linkage studies in BMI and obesity. Obesity Res 15:2263–2275

    Google Scholar 

  • Saxena R, Hivert MF, Langenberg C et al (2010) Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. Nat Genet 42:142–148

    PubMed  CAS  Google Scholar 

  • Scheer FAJL, Hilton MF, Mantzoros CS et al (2009) Adverse metabolic and cardiovascular consequences of circadian misalignment. PNAS 106:4453–4458

    PubMed  CAS  Google Scholar 

  • Scherag A, Dina C, Hinney A et al (2010) Two new loci for body-weight regulation identified in a joint analysis of genome-wide association studies for early-onset extreme obesity in French and German study groups. PLoS Genet 6:e1000916

    PubMed  Google Scholar 

  • Scuteri A, Sanna S, Chen W-M et al (2007) Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLos Genet 3:e115

    PubMed  Google Scholar 

  • Shi J, Long J, Gao YT et al (2010) Evaluation of genetic susceptibility loci for obesity in Chinese women. Am J Epidemiol 172:244–254

    PubMed  Google Scholar 

  • Shiri-Sverdlov R, Custers A, van Vliet-Ostaptchouk JV et al (2006) Identification of TUB as a novel candidate gene influencing body weight in humans. Diabetes 55:385–389

    PubMed  CAS  Google Scholar 

  • Shugart YY, Chen L, Day INM et al (2009) Two British women studies replicated the association between the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) and BMI. Eur J Hum Genet 17:1050–1055

    PubMed  CAS  Google Scholar 

  • Silha JV, Krsek M, Sucharda P et al (2005) Angiogenic factors are elevated in overweight and obese individuals. Int J Obes Relat Metab Disord 29:1308–1314

    CAS  Google Scholar 

  • Silventoinen K, Rokholm B, Kaprio J et al (2009) The genetic and environmental influences on childhood obesity: a systematic review of twin and adoption studies. Int J Obes 34:29–40

    Google Scholar 

  • Snieder H, Wang X, Shiri-Sverdlov R et al (2008) TUB is a candidate gene for late-onset obesity in women. Diabetologia 51:54–61

    PubMed  CAS  Google Scholar 

  • Sonestedt E, Roos C, Gullberg B et al (2009) Fat and carbohydrate intake modify the association between genetic variation in the FTO genotype and obesity. Am J Clinical Nutrition 90:1418–1425

    CAS  Google Scholar 

  • Sparso T, Hussain MS, Andersen G et al (2007) Relationships between the functional PPAR[alpha] Leu162Val polymorphism and obesity, type 2 diabetes, dyslipidaemia, and related quantitative traits in studies of 5799 middle-aged white people. Mol Genet Metab 90:205–209

    PubMed  CAS  Google Scholar 

  • Speakman JR, Rance KA, Johnstone AM (2008) Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure. Obesity Res 16:1961–1965

    CAS  Google Scholar 

  • Speliotes EK, Willer CJ, Berndt SI et al (2010) Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet 42:937–948

    PubMed  CAS  Google Scholar 

  • Stratigopoulos G, Padilla S, LeDuc CA et al (2008) Regulation of Fto/Ftm gene expression in mice and humans. Am J Physiol Regul Integr Comp Physiol 294:R1185–R1196

    PubMed  CAS  Google Scholar 

  • Stratigopoulos G, LeDuc CA, Cremona ML et al (2011) Cut-like homeobox 1 (CUX1) regulates expression of the fat mass and obesity-associated and retinitis pigmentosa GTPase regulator- interacting protein-1-like (RPGRIP1L) genes and coordinates leptin receptor signaling. J Biol Chem 286:2155–2170

    Google Scholar 

  • Stutzmann F, Vatin V, Cauchi S et al (2007) Non-synonymous polymorphisms in melanocortin-4 receptor protect against obesity: The two facets of a Janus obesity gene. Hum Mol Genet 16:1837–1844

    PubMed  CAS  Google Scholar 

  • Sudmant PH, Kitzman JO, Antonacci F et al (2010) Diversity of human copy number variation and multicopy genes. Science 330:641–646

    PubMed  CAS  Google Scholar 

  • Szopa M, Meirhaeghe A, Luan J et al (2010) No association between polymorphisms in the INSIG1 gene and the risk of type 2 diabetes and related traits. Am J Clin Nutr 92:252–257

    PubMed  CAS  Google Scholar 

  • Tabara Y, Osawa H, Guo H et al (2009) Prognostic significance of FTO genotype in the development of obesity in Japanese: the J-SHIPP study. Int J Obes 33:1243–1248

    CAS  Google Scholar 

  • Tan JT, Dorajoo R, Seielstad M et al (2008) FTO variants are associated with obesity in the Chinese and Malay populations in Singapore. Diabetes 57:2851–2857

    PubMed  CAS  Google Scholar 

  • The International HapMap Consortium (2007) A second generation human haplotype map of over 3.1 million SNPs. Nature 449:851–861

    Google Scholar 

  • Thorleifsson G, Walters GB, Gudbjartsson DF et al (2009) Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat Genet 41:18–24

    PubMed  CAS  Google Scholar 

  • Timpson NJ, Emmett PM, Frayling TM et al (2008) The fat mass-and obesity-associated locus and dietary intake in children. Am J Clin Nutr 88:971–978

    PubMed  CAS  Google Scholar 

  • Tonjes A, Scholz M, Loeffler M et al (2006) Association of Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma with Pre-diabetic phenotypes: Meta-analysis of 57 studies on nondiabetic individuals. Diabetes Care 29:2489–2497

    PubMed  Google Scholar 

  • Torekov SS, Larsen LH, Glumer C et al (2005) Evidence of an association between the Arg72 allele of the peptide YY and increased risk of Type 2 diabetes. Diabetes 54:2261–2265

    PubMed  CAS  Google Scholar 

  • Torekov S, Larsen L, Andersen G et al (2006) Variants in the 5∋ region of the neuropeptide Y receptor Y2 gene (NPY2R) are associated with obesity in 5,971 white subjects. Diabetologia 49:2653–2658

    PubMed  CAS  Google Scholar 

  • Tung YCL, Ayuso E, Shan X et al (2010) Hypothalamic-specific manipulation of FTO, the ortholog of the human obesity gene FTO, affects food intake in rats. PLoS ONE 5:e8771

    PubMed  Google Scholar 

  • Umekawa T, Yoshida T, Sakane N et al (1999) Trp64Arg mutation of beta3-adrenoceptor gene deteriorates lipolysis induced by beta3-adrenoceptor agonist in human omental adipocytes. Diabetes 48:117–120

    PubMed  CAS  Google Scholar 

  • Unger TJ, Calderon GA, Bradley LC et al (2007) Selective deletion of Bdnf in the ventromedial and dorsomedial hypothalamus of adult mice results in hyperphagic behavior and obesity. J Neurosci 27:14265–14274

    PubMed  CAS  Google Scholar 

  • Urhammer SA, Hansen T, Borch-Johnsen K et al (2000) Studies of the synergistic effect of the Trp/Arg64 polymorphism of the β3-adrenergic receptor gene and the −3826 A-  >  G variant of the uncoupling protein-1 gene on features of obesity and insulin resistance in a population-based sample of 379 young Danish subjects. J Clin Endocrinol Metab 85:3151–3154

    PubMed  CAS  Google Scholar 

  • Vaisse C, Clement K, Durand E et al (2000) Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity. J Clin Invest 106:253–262

    PubMed  CAS  Google Scholar 

  • van Vliet-Ostaptchouk JV, Onland-Moret NC, Shiri-Sverdlov R et al (2008) Polymorphisms of the TUB gene are associated with body composition and eating behavior in middle-aged women. PLoS ONE 3:e1405

    PubMed  Google Scholar 

  • Vimaleswaran KS, Li S, Zhao JH et al (2009) Physical activity attenuates the body mass index increasing influence of genetic variation in the FTO gene. Am J Clin Nutr 90:425–428

    PubMed  CAS  Google Scholar 

  • Vimaleswaran KS, Zhao JH, Wainwright NW et al (2010) Association between serotonin 5-HT-2 C receptor gene (HTR2C) polymorphisms and obesity- and mental health-related phenotypes in a large population-based cohort. Int J Obes 34:1028–1033

    CAS  Google Scholar 

  • Voight BF, Scott LJ, Steinthorsdottir V et al (2010) Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat Genet 42:579–589

    PubMed  CAS  Google Scholar 

  • Wahlen K, Sjolin E, Hoffstedt J (2007) The common rs9939609 gene variant of the fat mass and obesity associated gene (FTO) is related to fat cell lipolysis. J Lipid Res 49:607–611

    PubMed  Google Scholar 

  • Walston J, Silver K, Bogardus C et al (1995) Time of onset of non-insulin-dependent diabetes mellitus and genetic variation in the {beta}3-adrenergic-receptor gene. N Engl J Med 333:343–347

    PubMed  CAS  Google Scholar 

  • Walters RG, Jacquemont S, Valsesia A et al (2010) A new highly penetrant form of obesity due to deletions on chromosome 16p11.2. Nature 463:671–675

    PubMed  CAS  Google Scholar 

  • Wang C, Bomberg E, Levine A et al (2007) Brain-derived neurotrophic factor in the ventromedial nucleus of the hypothalamus reduces energy intake. Am J Physiol Regul Integr Comp Physiol 293:R1037–R1045

    PubMed  CAS  Google Scholar 

  • Wang D, Ma J, Zhang S et al (2010) Association of the MC4R V103I polymorphism with obesity: A Chinese case-control study and meta-analysis in 55,195 individuals. Obesity Res 18:573–579

    Google Scholar 

  • Wardle J, Llewellyn C, Sanderson S et al (2008a) The FTO gene and measured food intake in children. Int J Obes 33:42–45

    Google Scholar 

  • Wardle J, Carnell S, Haworth CMA et al (2008b) Obesity associated genetic variation in FTO is associated with diminished satiety. J Clin Endocrinol Metab 93:3640–3643

    PubMed  CAS  Google Scholar 

  • Weedon MN, Shields B, Hitman G et al (2006) No evidence of association of ENPP1 variants with Type 2 diabetes or obesity in a study of 8,089 U.K. Caucasians. Diabetes 55:3175–3179

    PubMed  CAS  Google Scholar 

  • Whitaker RC, Wright JA, Pepe MS et al (1997) Predicting obesity in young adulthood from childhood and parental obesity. N Engl J Med 337:869–873

    PubMed  CAS  Google Scholar 

  • Widen E, Lehto M, Kanninen T et al (1995) Association of a polymorphism in the β3-adrenergic-receptor gene with features of the insulin resistance syndrome in finns. N Engl J Med 333:348–352

    PubMed  CAS  Google Scholar 

  • Willer CJ, Speliotes EK, Loos RJF et al (2009) Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet 41:25–34

    PubMed  CAS  Google Scholar 

  • Wing MR, Ziegler JM, Langefeld CD et al. (2010) Analysis of FTO gene variants with obesity and glucose homeostasis measures in the multiethnic Insulin Resistance Atherosclerosis Study cohort. Int J Obes (online)

    Google Scholar 

  • Wong MY, Day NE, Luan JA et al (2003) The detection of gene-environment interaction for continuous traits: Should we deal with measurement error by bigger studies or better measurement? Int J Epidemiol 32:51–57

    PubMed  CAS  Google Scholar 

  • World Health Organisation. Obesity and overweight - Fact sheet N°311. 2006. World Health Organisation.

    Google Scholar 

  • Wu L, Xi B, Zhang M et al (2010) Associations of six single nucleotide polymorphisms in obesity-related genes with BMI and risk of obesity in Chinese children. Diabetes 59:3085–3089

    PubMed  CAS  Google Scholar 

  • Xi B, Shen Y, Zhang M et al (2010) The common rs9939609 variant of the fat mass and obesity-associated gene is associated with obesity risk in children and adolescents of Beijing. China BMC Med Genet 11:107

    Google Scholar 

  • Xiang Z, Litherland SA, Sorensen NB et al (2006) Pharmacological characterization of 40 human melanocortin-4 receptor polymorphisms with the endogenous proopiomelanocortin-derived Agonists and the Agouti-Related Protein (AGRP) Antagonist. Biochemistry 45:7277–7288

    PubMed  CAS  Google Scholar 

  • Xie C, Turley SD, Pentchev PG et al (1999) Cholesterol balance and metabolism in mice with loss of function of Niemann-Pick C protein. Am J Physiol – Endocrinol Metab 276:E336–E344

    CAS  Google Scholar 

  • Xu B, Goulding EH, Zang K et al (2003) Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor. Nat Neurosci 6:736–742

    PubMed  CAS  Google Scholar 

  • Yajnik C, Janipalli C, Bhaskar S et al (2009) FTO gene variants are strongly associated with type 2 diabetes in South Asian Indians. Diabetologia 52:247–252

    PubMed  CAS  Google Scholar 

  • Young EH, Wareham NJ, Farooqi S et al (2007) The V103I polymorphism of the MC4R gene and obesity: Population based studies and meta-analysis of 29,563 individuals. Int J Obes 31:1437–1441

    CAS  Google Scholar 

  • Zhao J, Bradfield JP, Li M et al (2009) The role of obesity-associated loci identified in genome-wide association studies in the determination of pediatric BMI. Obesity Res 17:2254–2257

    Google Scholar 

  • Zhao J, Bradfield JP, Zhang H et al (2010a) Examination of all Type 2 diabetes GWAS loci reveals HHEX-IDE as a locus influencing pediatric BMI. Diabetes 59:751–755

    PubMed  CAS  Google Scholar 

  • Zhao T, Zhao J, Lv J et al. (2010b) Meta-analysis on the effect of the Ala54Thr polymorphism of the fatty acid-binding protein 2 gene on body mass index. Nutr, Metab Cardiovasc Dis, in press

    Google Scholar 

  • Ziegler A, Schafer H, Hebebrand J (1997) Risch’s lambda values for human obesity estimated from segregation analysis. Int J Obes 21:952–953

    CAS  Google Scholar 

  • Zobel D, Andreasen C, Burgdorf K et al (2009a) Variation in the gene encoding Kruppel-like factor 7 influences body fat: Studies of 14,818 Danes. Eur J Endocrinol 160:603–609

    PubMed  CAS  Google Scholar 

  • Zobel DP, Andreasen CH, Grarup N et al (2009b) Variants near MC4R are associated with obesity and influence obesity-related quantitative traits in a population of middle-aged people: Studies of 14,940 Danes. Diabetes 58:757–764

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ruth J. F. Loos .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Loos, R.J.F. (2012). The Genetic Determinants of Common Obesity-Susceptibility. In: Symonds, M. (eds) Adipose Tissue Biology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0965-6_10

Download citation

Publish with us

Policies and ethics