Skip to main content
Log in

Advancement in genetic variants conferring obesity susceptibility from genome-wide association studies

  • Review
  • Published:
Frontiers of Medicine Aims and scope Submit manuscript

Abstract

Obesity prevalence has increased in recent years. Lifestyle change fuels obesity, but genetic factors cause more than 50% of average variations in obesity. The advent of genome-wide association studies (GWAS) has hastened the progress of polygenic obesity research. As of this writing, more than 73 obesity susceptibility loci have been identified in ethnic groups through GWAS. The identified loci explain only 2% to 4% of obesity heritability, thereby indicating that a large proportion of loci remain undiscovered. Thus, the next step is to identify and confirm novel loci, which may exhibit smaller effects and lower allele frequencies than established loci. However, achieving these tasks has been difficult for researchers. GWAS help researchers discover the causal loci. Moreover, numerous biological studies have been performed on the polygenic effects on obesity, such as studies on fat mass- and obesity-associated gene (FTO), but the role of these polygenic effects in the mechanism of obesity remains unclear. Thus, obesity-causing variations should be identified, and insights into the biology of polygenic effects on obesity are needed.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Patel P, Abate N. Body fat distribution and insulin resistance. Nutrients 2013; 5(6): 2019–2027

    Article  PubMed Central  PubMed  Google Scholar 

  2. Hou X, Lu J, Weng J, Ji L, Shan Z, Liu J, Tian H, Ji Q, Zhu D, Ge J, Lin L, Chen L, Guo X, Zhao Z, Li Q, Zhou Z, Shan G, Yang Z, Yang W, Jia W; China National Diabetes and Metabolic Disorders Study Group. Impact of waist circumference and body mass index on risk of cardiometabolic disorder and cardiovascular disease in Chinese adults: a national diabetes and metabolic disorders survey. PLoS ONE 2013; 8(3): e57319

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Maes HH, Neale MC, Eaves LJ. Genetic and environmental factors in relative body weight and human adiposity. Behav Genet 1997; 27(4): 325–351

    Article  CAS  PubMed  Google Scholar 

  4. Elks CE, den Hoed M, Zhao JH, Sharp SJ, Wareham NJ, Loos RJ, Ong KK. Variability in the heritability of body mass index: a systematic review and meta-regression. Front Endocrinol 2012; 3: 29

    Article  Google Scholar 

  5. 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. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 2007; 316(5826): 889–894

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Loos RJ, Lindgren CM, Li S, Wheeler E, Zhao JH, Prokopenko I, Inouye M, Freathy RM, Attwood AP, Beckmann JS, Berndt SI, 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, 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, Randall JC, Rayner NW, Ring SM, Sandhu MS, Scherag A, Sims MA, Song K, Soranzo N, Speliotes EK, Syddall HE, Teichmann SA, Timpson NJ, Tobias JH, Uda M, Vogel CI, Wallace C, Waterworth DM, Weedon MN, Willer CJ, 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. Common variants near MC4R are associated with fat mass weight and risk of obesity. Nat Genet 2008; 40(6): 768–775

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. 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, 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. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet 2009; 41(1): 25–34

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. 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. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat Genet 2009; 41(1): 18–24

    Article  CAS  PubMed  Google Scholar 

  9. 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, 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, 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. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet 2010; 42(11): 937–948

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. 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. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet 2007; 3(7): e115

    Article  PubMed Central  PubMed  Google Scholar 

  11. 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. Role of BMI-associated loci identified in GWAS meta-analyses in the context of common childhood obesity in European Americans. Obesity (Silver Spring) 2011; 19(12): 2436–2439

    Article  CAS  Google Scholar 

  12. Liu G, Zhu H, Lagou V, Gutin B, Barbeau P, Treiber FA, Dong Y, Snieder H. Common variants near melanocortin 4 receptor are associated with general and visceral adiposity in European- and African-American youth. J Pediatr 2010; 156(4): 598–605 e591

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Li H, Kilpeläinen TO, Liu C, Zhu J, Liu Y, Hu C, Yang Z, Zhang W, Bao W, Cha S, Wu Y, Yang T, Sekine A, Choi BY, Yajnik CS, Zhou D, Takeuchi F, Yamamoto K, Chan JC, Mani KR, Been LF, Imamura M, Nakashima E, Lee N, Fujisawa T, Karasawa S, Wen W, Joglekar CV, Lu W, Chang Y, Xiang Y, Gao Y, Liu S, Song Y, Kwak SH, Shin HD, Park KS, Fall CH, Kim JY, Sham PC, Lam KS, Zheng W, Shu X, Deng H, Ikegami H, Krishnaveni GV, Sanghera DK, Chuang L, Liu L, Hu R, Kim Y, Daimon M, Hotta K, Jia W, Kooner JS, Chambers JC, Chandak GR, Ma RC, Maeda S, Dorajoo R, Yokota M, Takayanagi R, Kato N, Lin X, Loos RJ, Okada Y, Kubo M, Ohmiya H, Takahashi A, Kumasaka N, Hosono N, Maeda S, Wen W, Dorajoo R, Go MJ, Zheng W, Kato N, Wu JY, Lu Q, Tsunoda T, Yamamoto K, Nakamura Y, Kamatani N, Tanaka T. Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96, 551 East and South Asians. Diabetologia 2012; 55(4): 981–995

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Okada Y, Kubo M, Ohmiya H, Takahashi A, Kumasaka N, Hosono N, Maeda S, Wen W, Dorajoo R, Go MJ, Zheng W, Kato N, Wu JY, Lu Q, Tsunoda T, Yamamoto K, Nakamura Y, Kamatani N, Tanaka T. Common variants at CDKAL1 and KLF9 are associated with body mass index in east Asian populations. Nat Genet 2012; 44(3): 302–306

    Article  CAS  PubMed  Google Scholar 

  15. 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, Wu JY, Lee JY, Hu FB, Tanaka T, Tai ES, Shu XO. Meta-analysis identifies common variants associated with body mass index in east Asians. Nat Genet 2012; 44(3): 307–311

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Wen W, Zheng W, Okada Y, Takeuchi F, Tabara Y, Hwang JY, Dorajoo R, Li H, Tsai FJ, Yang X, He J, Wu Y, He M, Zhang Y, Liang J, Guo X, Sheu WH, Delahanty R, Guo X, Kubo M, Yamamoto K, Ohkubo T, Go MJ, Liu JJ, Gan W, Chen CC, Gao Y, Li S, Lee NR, Wu C, Zhou X, Song H, Yao J, Lee IT, Long J, Tsunoda T, Akiyama K, Takashima N, Cho YS, Ong RT, Lu L, Chen CH, Tan A, Rice TK, Adair LS, Gui L, Allison M, Lee WJ, Cai Q, Isomura M, Umemura S, Kim YJ, Seielstad M, Hixson J, Xiang YB, Isono M, Kim BJ, Sim X, Lu W, Nabika T, Lee J, Lim WY, Gao YT, Takayanagi R, Kang DH, Wong TY, Hsiung CA, Wu IC, Juang JM, Shi J, Choi BY, Aung T, Hu F, Kim MK, Lim WY, Wang TD, Shin MH, Lee J, Ji BT, Lee YH, Young TL, Shin DH, Chun BY, Cho MC, Han BG, Hwu CM, Assimes TL, Absher D, Yan X, Kim E, Kuo JZ, Kwon S, Taylor KD, Chen YD, Rotter JI, Qi L, Zhu D, Wu T, Mohlke KL, Gu D, Mo Z, Wu JY, Lin X, Miki T, Tai ES, Lee JY, Kato N, Shu XO, Tanaka T. Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index. Hum Mol Genet 2014 May 26. [Epub ahead of print] doi: 10.1093/hmg/ddu248

    Google Scholar 

  17. Fitzgerald KR. Review of article: Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999–2010 by Katherine M. Flegal, PhD; Margaret D. Carroll, MSPH; Brian K. Kit, MD; Cynthia L. Ogden, PhD (JAMA 2012;307:491-7). J Vasc Nurs 2013; 31(3): 131–132

    Article  PubMed  Google Scholar 

  18. Ng MC, Hester JM, Wing MR, Li J, Xu J, Hicks PJ, Roh BH, Lu L, Divers J, Langefeld CD, Freedman BI, Palmer ND, Bowden DW. Genome-wide association of BMI in African Americans. Obesity (Silver Spring) 2012; 20(3): 622–627

    Article  CAS  Google Scholar 

  19. 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, Kooperberg C, Papanicolaou GJ, Henderson BE, Reiner AP, Hirschhorn JN, Loos RJ, North KE, Haiman CA. A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry. Nat Genet 2013; 45(6): 690–696

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. 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. Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile. Nat Genet 2011; 43(8): 753–760

    Article  PubMed Central  PubMed  Google Scholar 

  21. Folsom AR, Kushi LH, Anderson KE, Mink PJ, Olson JE, Hong CP, Sellers TA, Lazovich D, Prineas RJ. Associations of general and abdominal obesity with multiple health outcomes in older women: the Iowa Women’s Health Study. Arch Intern Med 2000; 160(14): 2117–2128

    Article  CAS  PubMed  Google Scholar 

  22. Cassano PA, Rosner B, Vokonas PS, Weiss ST. Obesity and body fat distribution in relation to the incidence of non-insulin-dependent diabetes mellitus. A prospective cohort study of men in the normative aging study. Am J Epidemiol 1992; 136(12): 1474–1486

    CAS  PubMed  Google Scholar 

  23. Pischon T, Boeing H, Hoffmann K, Bergmann M, Schulze MB, Overvad K, van der Schouw YT, Spencer E, Moons KG, Tjønneland A, Halkjaer J, Jensen MK, Stegger J, Clavel-Chapelon F, Boutron-Ruault MC, Chajes V, Linseisen J, Kaaks R, Trichopoulou A, Trichopoulos D, Bamia C, Sieri S, Palli D, Tumino R, Vineis P, Panico S, Peeters PH, May AM, Bueno-de-Mesquita HB, van Duijnhoven FJ, Hallmans G, Weinehall L, Manjer J, Hedblad B, Lund E, Agudo A, Arriola L, Barricarte A, Navarro C, Martinez C, Quirós JR, Key T, Bingham S, Khaw KT, Boffetta P, Jenab M, Ferrari P, Riboli E. General and abdominal adiposity and risk of death in Europe. N Engl J Med 2008; 359(20): 2105–2120

    Article  CAS  PubMed  Google Scholar 

  24. 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. NRXN3 is a novel locus for waist circumference: a genome-wide association study from the CHARGE Consortium. PLoS Genet 2009; 5(6): e1000539

    Article  PubMed Central  PubMed  Google Scholar 

  25. 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, 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, Hugh Watkins, 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. Genome-wide association scan metaanalysis identifies three Loci influencing adiposity and fat distribution. PLoS Genet 2009; 5(6): e1000508

    Article  PubMed Central  PubMed  Google Scholar 

  26. Rose KM, Newman B, Mayer-Davis EJ, Selby JV. Genetic and behavioral determinants of waist-hip ratio and waist circumference in women twins. Obes Res 1998; 6(6): 383–392

    Article  CAS  PubMed  Google Scholar 

  27. 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, 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. Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Nat Genet 2010; 42(11): 949–960

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Randall JC, Winkler TW, Kutalik Z, Berndt SI, Jackson AU, Monda KL, Kilpeläinen TO, Esko T, Mägi R, Li S, Workalemahu T, Feitosa MF, Croteau-Chonka DC, Day FR, Fall T, Ferreira T, Gustafsson S, Locke AE, Mathieson I, Scherag A, Vedantam S, Wood AR, Liang L, Steinthorsdottir V, Thorleifsson G, Dermitzakis ET, Dimas AS, Karpe F, Min JL, Nicholson G, Clegg DJ, Person T, Krohn JP, Bauer S, Buechler C, Eisinger K, Bonnefond A, Froguel P, Hottenga JJ, Prokopenko I, Waite LL, Harris TB, Smith AV, Shuldiner AR, McArdle WL, Caulfield MJ, Munroe PB, Grönberg H, Chen YD, Li G, Beckmann JS, Johnson T, Thorsteinsdottir U, Teder-Laving M, Khaw KT, Wareham NJ, Zhao JH, Amin N, Oostra BA, Kraja AT, Province MA, Cupples LA, Heard-Costa NL, Kaprio J, Ripatti S, Surakka I, Collins FS, Saramies J, Tuomilehto J, Jula A, Salomaa V, Erdmann J, Hengstenberg C, Loley C, Schunkert H, Lamina C, Wichmann HE, Albrecht E, Gieger C, Hicks AA, Johansson A, Pramstaller PP, Kathiresan S, Speliotes EK, Penninx B, Hartikainen AL, Jarvelin MR, Gyllensten U, Boomsma DI, Campbell H, Wilson JF, Chanock SJ, Farrall M, Goel A, Medina-Gomez C, Rivadeneira F, Estrada K, Uitterlinden AG, Hofman A, Zillikens MC, den Heijer M, Kiemeney LA, Maschio A, Hall P, Tyrer J, Teumer A, Völzke H, Kovacs P, Tönjes A, Mangino M, Spector TD, Hayward C, Rudan I, Hall AS, Samani NJ, Attwood AP, Sambrook JG, Hung J, Palmer LJ, Lokki ML, Sinisalo J, Boucher G, Huikuri H, Lorentzon M, Ohlsson C, Eklund N, Eriksson JG, Barlassina C, Rivolta C, Nolte IM, Snieder H, Van der Klauw MM, Van Vliet-Ostaptchouk JV, Gejman PV, Shi J, Jacobs KB, Wang Z, Bakker SJ, Mateo Leach I, Navis G, van der Harst P, Martin NG, Medland SE, Montgomery GW, Yang J, Chasman DI, Ridker PM, Rose LM, Lehtimäki T, Raitakari O, Absher D, Iribarren C, Basart H, Hovingh KG, Hyppönen E, Power C, Anderson D, Beilby JP, Hui J, Jolley J, Sager H, Bornstein SR, Schwarz PE, Kristiansson K, Perola M, Lindström J, Swift AJ, Uusitupa M, Atalay M, Lakka TA, Rauramaa R, Bolton JL, Fowkes G, Fraser RM, Price JF, Fischer K, Krjutå Kov K, Metspalu A, Mihailov E, Langenberg C, Luan J, Ong KK, Chines PS, Keinanen-Kiukaanniemi SM, Saaristo TE, Edkins S, Franks PW, Hallmans G, Shungin D, Morris AD, Palmer CN, Erbel R, Moebus S, Nöthen MM, Pechlivanis S, Hveem K, Narisu N, Hamsten A, Humphries SE, Strawbridge RJ, Tremoli E, Grallert H, Thorand B, Illig T, Koenig W, Müller-Nurasyid M, Peters A, Boehm BO, Kleber ME, März W, Winkelmann BR, Kuusisto J, Laakso M, Arveiler D, Cesana G, Kuulasmaa K, Virtamo J, Yarnell JW, Kuh D, Wong A, Lind L, de Faire U, Gigante B, Magnusson PK, Pedersen NL, Dedoussis G, Dimitriou M, Kolovou G, Kanoni S, Stirrups K, Bonnycastle LL, Njølstad I, Wilsgaard T, Ganna A, Rehnberg E, Hingorani A, Kivimaki M, Kumari M, Assimes TL, Barroso I, Boehnke M, Borecki IB, Deloukas P, Fox CS, Frayling T, Groop LC, Haritunians T, Hunter D, Ingelsson E, Kaplan R, Mohlke KL, O’Connell JR, Schlessinger D, Strachan DP, Stefansson K, van Duijn CM, Abecasis GR, McCarthy MI, Hirschhorn JN, Qi L, Loos RJ, Lindgren CM, North KE, Heid IM. Sex-stratified genome-wide association studies including 270, 000 individuals show sexual dimorphism in genetic loci for anthropometric traits. PLoS Genet 2013; 9(6): e1003500

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Chambers JC, Elliott P, Zabaneh D, Zhang W, Li Y, Froguel P, Balding D, Scott J, Kooner JS. Common genetic variation near MC4R is associated with waist circumference and insulin resistance. Nat Genet 2008; 40(6): 716–718

    Article  CAS  PubMed  Google Scholar 

  30. Cho YS, Go MJ, Kim YJ, Heo JY, Oh JH, Ban HJ, Yoon D, Lee MH, Kim DJ, Park M, Cha SH, Kim JW, Han BG, Min H, Ahn Y, Park MS, Han HR, Jang HY, Cho EY, Lee JE, Cho NH, Shin C, Park T, Park JW, Lee JK, Cardon L, Clarke G, McCarthy MI, Lee JY, Lee JK, Oh B, Kim HL. A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits. Nat Genet 2009; 41(5): 527–534

    Article  CAS  PubMed  Google Scholar 

  31. Liu CT, Monda KL, Taylor KC, Lange L, Demerath EW, Palmas W, Wojczynski MK, Ellis JC, Vitolins MZ, Liu S, Papanicolaou GJ, Irvin MR, Xue L, Griffin PJ, Nalls MA, Adeyemo A, Liu J, Li G, Ruiz-Narvaez EA, Chen WM, Chen F, Henderson BE, Millikan RC, Ambrosone CB, Strom SS, Guo X, Andrews JS, Sun YV, Mosley TH, Yanek LR, Shriner D, Haritunians T, Rotter JI, Speliotes EK, Smith M, Rosenberg L, Mychaleckyj J, Nayak U, Spruill I, Garvey WT, Pettaway C, Nyante S, Bandera EV, Britton AF, Zonderman AB, Rasmussen-Torvik LJ, Chen YD, Ding J, Lohman K, Kritchevsky SB, Zhao W, Peyser PA, Kardia SL, Kabagambe E, Broeckel U, Chen G, Zhou J, Wassertheil-Smoller S, Neuhouser ML, Rampersaud E, Psaty B, Kooperberg C, Manson JE, Kuller LH, Ochs-Balcom HM, Johnson KC, Sucheston L, Ordovas JM, Palmer JR, Haiman CA, McKnight B, Howard BV, Becker DM, Bielak LF, Liu Y, Allison MA, Grant SF, Burke GL, Patel SR, Schreiner PJ, Borecki IB, Evans MK, Taylor H, Sale MM, Howard V, Carlson CS, Rotimi CN, Cushman M, Harris TB, Reiner AP, Cupples LA, North KE, Fox CS. Genome-wide association of body fat distribution in African ancestry populations suggests new loci. PLoS Genet 2013; 9(8): e1003681

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Matsuzawa Y, Shimomura I, Nakamura T, Keno Y, Kotani K, Tokunaga K. Pathophysiology and pathogenesis of visceral fat obesity. Obes Res 1995; 3(Suppl 2): 187S–194S

    Article  PubMed  Google Scholar 

  33. Després JP, Nadeau A, Tremblay A, Ferland M, Moorjani S, Lupien PJ, Thériault G, Pinault S, Bouchard C. Role of deep abdominal fat in the association between regional adipose tissue distribution and glucose tolerance in obese women. Diabetes 1989; 38(3): 304–309

    Article  PubMed  Google Scholar 

  34. Bluher M. Adipose tissue dysfunction in obesity. Exp Clin Endocrinol Diabetes 2009; 117(6): 241–250

    Article  CAS  PubMed  Google Scholar 

  35. Fox CS, Liu Y, White CC, Feitosa M, Smith AV, Heard-Costa N, Lohman K, Johnson AD, Foster MC, Greenawalt DM, Griffin P, Ding J, Newman AB, Tylavsky F, Miljkovic I, Kritchevsky SB, Launer L, Garcia M, Eiriksdottir G, Carr JJ, Gudnason V, Harris TB, Cupples LA, Borecki IB. Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women. PLoS Genet 2012; 8(5): e1002695

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. 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. Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet 2007; 39(6): 724–726

    Article  CAS  PubMed  Google Scholar 

  37. Meyre D, Delplanque J, Chèvre JC, Lecoeur C, Lobbens S, Gallina S, Durand E, Vatin V, Degraeve F, Proença C, Gaget S, Körner A, Kovacs P, Kiess W, Tichet J, Marre M, Hartikainen AL, Horber F, Potoczna N, Hercberg S, Levy-Marchal C, Pattou F, Heude B, Tauber M, McCarthy MI, Blakemore AI, Montpetit A, Polychronakos C, Weill J, Coin LJ, Asher J, Elliott P, Järvelin MR, Visvikis-Siest S, Balkau B, Sladek R, Balding D, Walley A, Dina C, Froguel P. Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations. Nat Genet 2009; 41(2): 157–159

    Article  CAS  PubMed  Google Scholar 

  38. Cecil JE, Tavendale R, Watt P, Hetherington MM, Palmer CN. An obesity-associated FTO gene variant and increased energy intake in children. N Engl J Med 2008; 359(24): 2558–2566

    Article  CAS  PubMed  Google Scholar 

  39. Tanofsky-Kraff M, Han JC, Anandalingam K, Shomaker LB, Columbo KM, Wolkoff LE, Kozlosky M, Elliott C, Ranzenhofer LM, Roza CA, Yanovski SZ, Yanovski JA. The FTO gene rs9939609 obesity-risk allele and loss of control over eating. Am J Clin Nutr 2009; 90(6): 1483–1488

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Wardle J, Carnell S, Haworth CM, Farooqi IS, O’Rahilly S, Plomin R. Obesity associated genetic variation in FTO is associated with diminished satiety. J Clin Endocrinol Metab 2008; 93(9): 3640–3643

    Article  CAS  PubMed  Google Scholar 

  41. Tanaka T, Ngwa JS, van Rooij FJ, Zillikens MC, Wojczynski MK, Frazier-Wood AC, Houston DK, Kanoni S, Lemaitre RN, Luan J, Mikkilä V, Renstrom F, Sonestedt E, Zhao JH, Chu AY, Qi L, Chasman DI, de Oliveira Otto MC, Dhurandhar EJ, Feitosa MF, Johansson I, Khaw KT, Lohman KK, Manichaikul A, McKeown NM, Mozaffarian D, Singleton A, Stirrups K, Viikari J, Ye Z, Bandinelli S, Barroso I, Deloukas P, Forouhi NG, Hofman A, Liu Y, Lyytikäinen LP, North KE, Dimitriou M, Hallmans G, Kähönen M, Langenberg C, Ordovas JM, Uitterlinden AG, Hu FB, Kalafati IP, Raitakari O, Franco OH, Johnson A, Emilsson V, Schrack JA, Semba RD, Siscovick DS, Arnett DK, Borecki IB, Franks PW, Kritchevsky SB, Lehtimäki T, Loos RJ, Orho-Melander M, Rotter JI, Wareham NJ, Witteman JC, Ferrucci L, Dedoussis G, Cupples LA, Nettleton JA. Genome-wide meta-analysis of observational studies shows common genetic variants associated with macronutrient intake. Am J Clin Nutr 2013; 97(6): 1395–1402

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Karra E, O’Daly OG, Choudhury AI, Yousseif A, Millership S, Neary MT, Scott WR, Chandarana K, Manning S, Hess ME, Iwakura H, Akamizu T, Millet Q, Gelegen C, Drew ME, Rahman S, Emmanuel JJ, Williams SC, Rüther UU, Brüning JC, Withers DJ, Zelaya FO, Batterham RL. A link between FTO, ghrelin, and impaired brain food-cue responsivity. J Clin Invest 2013; 123(8): 3539–3551

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Llewellyn CH, Trzaskowski M, van Jaarsveld CH, Plomin R, Wardle J. Satiety mechanisms in genetic risk of obesity. JAMA Pediatr 2014; 168(4): 338–344

    Article  PubMed Central  PubMed  Google Scholar 

  44. Ahmad T, Chasman DI, Mora S, Paré G, Cook NR, Buring JE, Ridker PM, Lee IM. The fat-mass and obesity-associated (FTO) gene, physical activity, and risk of incident cardiovascular events in white women. Am Heart J 2010; 160(6): 1163–1169

    Article  PubMed Central  PubMed  Google Scholar 

  45. Holzapfel C, Grallert H, Huth C, Wahl S, Fischer B, Doring A, Ruckert IM, Hinney A, Hebebrand J, Wichmann HE, Hauner H, Illig T, Heid IM. Genes and lifestyle factors in obesity: results from 12, 462 subjects from MONICA/KORA. Int J Obes (Lond) 2010; 34(10): 1538–1545

    Article  CAS  Google Scholar 

  46. 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. Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218, 166 adults and 19, 268 children. PLoS Med 2011; 8(11): e1001116

    Article  PubMed Central  PubMed  Google Scholar 

  47. Karasawa S, Daimon M, Sasaki S, Toriyama S, Oizumi T, Susa S, Kameda W, Wada K, Muramatsu M, Fukao A, Kubota I, Kawata S, Kayama T, Kato T. Association of the common fat mass and obesity associated (FTO) gene polymorphism with obesity in a Japanese population. Endocr J 2010; 57(4): 293–301

    Article  CAS  PubMed  Google Scholar 

  48. Ahmad T, Lee IM, Paré G, Chasman DI, Rose L, Ridker PM, Mora S. Lifestyle interaction with fat mass and obesity-associated (FTO) genotype and risk of obesity in apparently healthy U.S. women. Diabetes Care 2011; 34(3): 675–680

    Article  PubMed Central  PubMed  Google Scholar 

  49. 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. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 2007; 318(5855): 1469–1472

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  50. Tung YC, Ayuso E, Shan X, Bosch F, O’Rahilly S, Coll AP, Yeo GS. Hypothalamic-specific manipulation of Fto, the ortholog of the human obesity gene FTO, affects food intake in rats. PLoS ONE 2010; 5(1): e8771

    Article  PubMed Central  PubMed  Google Scholar 

  51. Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T, Brüning JC, Rüther U. Inactivation of the Fto gene protects from obesity. Nature 2009; 458(7240): 894–898

    Article  CAS  PubMed  Google Scholar 

  52. Church C, Moir L, McMurray F, Girard C, Banks GT, Teboul L, Wells S, Brüning JC, Nolan PM, Ashcroft FM, Cox RD. Overexpression of Fto leads to increased food intake and results in obesity. Nat Genet 2010; 42(12): 1086–1092

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  53. Cheung MK, Gulati P, O’Rahilly S, Yeo GS. FTO expression is regulated by availability of essential amino acids. Int J Obes (Lond) 2013; 37(5): 744–747

    Article  CAS  Google Scholar 

  54. Wu Q, Saunders RA, Szkudlarek-Mikho M, Serna IL, Chin KV. The obesity-associated Fto gene is a transcriptional coactivator. Biochem Biophys Res Commun 2010; 401(3): 390–395

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  55. Smemo S, Tena JJ, Kim KH, Gamazon ER, Sakabe NJ, Gómez-Marín C, Aneas I, Credidio FL, Sobreira DR, Wasserman NF, Lee JH, Puviindran V, Tam D, Shen M, Son JE, Vakili NA, Sung HK, Naranjo S, Acemel RD, Manzanares M, Nagy A, Cox NJ, Hui CC, Gomez-Skarmeta JL, Nóbrega MA. Obesity-associated variants within FTO form long-range functional connections with IRX3. Nature 2014; 507(7492): 371–375

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  56. 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. Genome partitioning of genetic variation for complex traits using common SNPs. Nat Genet 2011; 43(6): 519–525

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  57. Llewellyn CH, Trzaskowski M, Plomin R, Wardle J. Finding the missing heritability in pediatric obesity: the contribution of genomewide complex trait analysis. Int J Obes (Lond) 2013; 37(11): 1506–1509

    Article  CAS  Google Scholar 

  58. Min J, Chiu DT, Wang Y. Variation in the heritability of body mass index based on diverse twin studies: a systematic review. Obes Rev 2013; 14(11): 871–882

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  59. Llewellyn CH, Trzaskowski M, van Jaarsveld CH, Plomin R, Wardle J. Satiety mechanisms in genetic risk of obesity. JAMA Pediatr 2014; 168(4): 338–344

    Article  PubMed Central  PubMed  Google Scholar 

  60. Zhu J, Zong G, Lu L, Gan W, Ji L, Hu R, Ye X, Sun L, Loos R J, Li H, Lin X. Association of genetic predisposition to obesity with type 2 diabetes risk in Han Chinese individuals.. Diabetologia 2014; 57(9): 1830–1833

    Article  CAS  PubMed  Google Scholar 

  61. Qi Q, Chu AY, Kang JH, Huang J, Rose LM, Jensen MK, Liang L, Curhan GC, Pasquale LR, Wiggs JL, De Vivo I, Chan AT, Choi HK, Tamimi RM, Ridker PM, Hunter DJ, Willett WC, Rimm EB, Chasman DI, Hu FB, Qi L. Fried food consumption, genetic risk, and body mass index: gene-diet interaction analysis in three US cohort studies. BMJ 2014; 348G1610

  62. Belsky DW, Moffitt TE, Sugden K, Williams B, Houts R, McCarthy J, Caspi A. Development and evaluation of a genetic risk score for obesity. Biodemography Soc Biol 2013; 59(1): 85–100

    Article  PubMed  Google Scholar 

  63. Simonson MA, McQueen MB, Keller MC. Whole-genome pathway analysis on 132, 497 individuals identifies novel gene-sets associated with body mass index. PLoS ONE 2014; 9(1): e78546

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Cheng Hu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, T., Jia, W. & Hu, C. Advancement in genetic variants conferring obesity susceptibility from genome-wide association studies. Front. Med. 9, 146–161 (2015). https://doi.org/10.1007/s11684-014-0373-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11684-014-0373-8

Keywords

Navigation