Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2013 Jun;45(6):690-6.
doi: 10.1038/ng.2608. Epub 2013 Apr 14.

A Meta-Analysis Identifies New Loci Associated With Body Mass Index in Individuals of African Ancestry

Keri L Monda  1 Gary K ChenKira C TaylorCameron PalmerTodd L EdwardsLeslie A LangeMaggie C Y NgAdebowale A AdeyemoMatthew A AllisonLawrence F BielakGuanjie ChenMariaelisa GraffMarguerite R IrvinSuhn K RhieGuo LiYongmei LiuYoufang LiuYingchang LuMichael A NallsYan V SunMary K WojczynskiLisa R YanekMelinda C AldrichAdeyinka AdemolaChristopher I AmosElisa V BanderaCathryn H BockAngela BrittonUlrich BroeckelQuiyin CaiNeil E CaporasoChris S CarlsonJohn CarptenGraham CaseyWei-Min ChenFang ChenYii-Der I ChenCharleston W K ChiangGerhard A CoetzeeEllen DemerathSandra L Deming-HalversonRyan W DriverPatricia DubbertMary F FeitosaYe FengBarry I FreedmanElizabeth M GillandersOmri GottesmanXiuqing GuoTalin HarituniansTamara HarrisCurtis C HarrisAnselm J M HennisDena G HernandezLorna H McNeillTimothy D HowardBarbara V HowardVirginia J HowardKaren C JohnsonSun J KangBrendan J KeatingSuzanne KolbLewis H KullerAbdullah KutlarCarl D LangefeldGuillaume LettreKurt LohmanVaneet LotayHelen LyonJoann E MansonWilliam MaixnerYan A MengKristine R MonroeImran Morhason-BelloAdam B MurphyJosyf C MychaleckyjRajiv NadukuruKatherine L NathansonUma NayakAmidou N'diayeBarbara NemesureSuh-Yuh WuM Cristina LeskeChristine Neslund-DudasMarian NeuhouserSarah NyanteHeather Ochs-BalcomAdesola OgunniyiTemidayo O OgundiranOladosu OjengbedeOlufunmilayo I OlopadeJulie R PalmerEdward A Ruiz-NarvaezNicholette D PalmerMichael F PressEvandine RampersaudLaura J Rasmussen-TorvikJorge L Rodriguez-GilBabatunde SalakoEric E SchadtAnn G SchwartzDaniel A ShrinerDavid SiscovickShad B SmithSylvia Wassertheil-SmollerElizabeth K SpeliotesMargaret R SpitzLara SuchestonHerman TaylorBamidele O TayoMargaret A TuckerDavid J Van Den BergDigna R Velez EdwardsZhaoming WangJohn K WienckeThomas W WinklerJohn S WitteMargaret WrenschXifeng WuJames J YangAlbert M LevinTaylor R YoungNeil A ZakaiMary CushmanKrista A ZanettiJing Hua ZhaoWei ZhaoYonglan ZhengJie ZhouRegina G ZieglerJoseph M ZmudaJyotika K FernandesGary S GilkesonDiane L KamenKelly J HuntIda J SpruillChristine B AmbrosoneStefan AmbsDonna K ArnettLarry AtwoodDiane M BeckerSonja I BerndtLeslie BernsteinWilliam J BlotIngrid B BoreckiErwin P BottingerDonald W BowdenGregory BurkeStephen J ChanockRichard S CooperJingzhong DingDavid DugganMichele K EvansCaroline FoxW Timothy GarveyJonathan P BradfieldHakon HakonarsonStruan F A GrantAnn HsingLisa ChuJennifer J HuDezheng HuoSue A InglesEsther M JohnJoanne M JordanEdmond K KabagambeSharon L R KardiaRick A KittlesPhyllis J GoodmanEric A KleinLaurence N KolonelLoic Le MarchandSimin LiuBarbara McKnightRobert C MillikanThomas H MosleyBadri PadhukasahasramL Keoki WilliamsSanjay R PatelUlrike PetersCurtis A PettawayPatricia A PeyserBruce M PsatySusan RedlineCharles N RotimiBenjamin A RybickiMichèle M SalePamela J SchreinerLisa B SignorelloAndrew B SingletonJanet L StanfordSara S StromMichael J ThunMara VitolinsWei ZhengJason H MooreScott M WilliamsShamika KetkarXiaofeng ZhuAlan B ZondermanNABEC ConsortiumUKBEC ConsortiumBioBank Japan ProjectAGEN ConsortiumCharles KooperbergGeorge J PapanicolaouBrian E HendersonAlex P ReinerJoel N HirschhornRuth J F LoosKari E NorthChristopher A Haiman
Affiliations
Free PMC article
Meta-Analysis

A Meta-Analysis Identifies New Loci Associated With Body Mass Index in Individuals of African Ancestry

Keri L Monda et al. Nat Genet. .
Free PMC article

Abstract

Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry and followed up the most significant associations in an additional 32,268 individuals of African ancestry. We identified one new locus at 5q33 (GALNT10, rs7708584, P = 3.4 × 10(-11)) and another at 7p15 when we included data from the GIANT consortium (MIR148A-NFE2L3, rs10261878, P = 1.2 × 10(-10)). We also found suggestive evidence of an association at a third locus at 6q16 in the African-ancestry sample (KLHL32, rs974417, P = 6.9 × 10(-8)). Thirty-two of the 36 previously established BMI variants showed directionally consistent effect estimates in our GWAS (binomial P = 9.7 × 10(-7)), five of which reached genome-wide significance. These findings provide strong support for shared BMI loci across populations, as well as for the utility of studying ancestrally diverse populations.

Figures

Figure 1
Figure 1
Manhattan plot displaying results of the BMI association meta-analysis in the Stage 1 studies. Colored genomic loci indicate novel associations (red) and those detected previously (blue).
Figure 2
Figure 2
Regional plots of three novel genome-wide significant loci identified in men and women of African ancestry. (a) rs7708584 (GALNT10 region), (b) rs974417 (KLHL32 region), and (c) rs10261878 (MIR148A/NFE2L3 region). For 2a and b, Stage 1 p-value represented by purple circle and Stage 1+2+3 p-value represented by purple square; for 2c, Stage 1 p-value represented by purple circle, African ancestry Stage 1+2+3 p-value represented by purple diamond, and African ancestry + GIANT p-value represented by purple square. SNPs are plotted by their position 500kb on either side of the index SNP on the chromosome against their association (−log10 P) with BMI using the Stage 1 data. SNPs surrounding the top SNPs are colored to indicate the local LD structure using pairwise r2 data from the May 2012 AFR panel of the 1000 genomes.
Figure 2
Figure 2
Regional plots of three novel genome-wide significant loci identified in men and women of African ancestry. (a) rs7708584 (GALNT10 region), (b) rs974417 (KLHL32 region), and (c) rs10261878 (MIR148A/NFE2L3 region). For 2a and b, Stage 1 p-value represented by purple circle and Stage 1+2+3 p-value represented by purple square; for 2c, Stage 1 p-value represented by purple circle, African ancestry Stage 1+2+3 p-value represented by purple diamond, and African ancestry + GIANT p-value represented by purple square. SNPs are plotted by their position 500kb on either side of the index SNP on the chromosome against their association (−log10 P) with BMI using the Stage 1 data. SNPs surrounding the top SNPs are colored to indicate the local LD structure using pairwise r2 data from the May 2012 AFR panel of the 1000 genomes.
Figure 2
Figure 2
Regional plots of three novel genome-wide significant loci identified in men and women of African ancestry. (a) rs7708584 (GALNT10 region), (b) rs974417 (KLHL32 region), and (c) rs10261878 (MIR148A/NFE2L3 region). For 2a and b, Stage 1 p-value represented by purple circle and Stage 1+2+3 p-value represented by purple square; for 2c, Stage 1 p-value represented by purple circle, African ancestry Stage 1+2+3 p-value represented by purple diamond, and African ancestry + GIANT p-value represented by purple square. SNPs are plotted by their position 500kb on either side of the index SNP on the chromosome against their association (−log10 P) with BMI using the Stage 1 data. SNPs surrounding the top SNPs are colored to indicate the local LD structure using pairwise r2 data from the May 2012 AFR panel of the 1000 genomes.
Figure 3
Figure 3
Effect estimates (95% CI) per BMI-increasing allele for the 3 novel loci discovered in individuals of African ancestry (1st section, in descending order of African effect size), the 32 loci discovered in individuals of European ancestry (2nd section, in descending order of European effect size), and the 4 loci discovered in individuals of Asian ancestry (3rd section, in descending order of Asian effect size). Results for individuals of African ancestry depicted by red dots (Stage 1+2+3 for novel loci, Stage 1 for previously-discovered loci); results for individuals of European ancestry depicted by black squares from Speliotes EK et al, 2010; and results for individuals of Asian ancestry depicted by green triangles from Okada Y et al, 2012 and Wen W et al, 2012.

Similar articles

  • Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African Ancestry Anthropometry Genetics Consortium.
    Ng MCY, Graff M, Lu Y, Justice AE, Mudgal P, Liu CT, Young K, Yanek LR, Feitosa MF, Wojczynski MK, Rand K, Brody JA, Cade BE, Dimitrov L, Duan Q, Guo X, Lange LA, Nalls MA, Okut H, Tajuddin SM, Tayo BO, Vedantam S, Bradfield JP, Chen G, Chen WM, Chesi A, Irvin MR, Padhukasahasram B, Smith JA, Zheng W, Allison MA, Ambrosone CB, Bandera EV, Bartz TM, Berndt SI, Bernstein L, Blot WJ, Bottinger EP, Carpten J, Chanock SJ, Chen YI, Conti DV, Cooper RS, Fornage M, Freedman BI, Garcia M, Goodman PJ, Hsu YH, Hu J, Huff CD, Ingles SA, John EM, Kittles R, Klein E, Li J, McKnight B, Nayak U, Nemesure B, Ogunniyi A, Olshan A, Press MF, Rohde R, Rybicki BA, Salako B, Sanderson M, Shao Y, Siscovick DS, Stanford JL, Stevens VL, Stram A, Strom SS, Vaidya D, Witte JS, Yao J, Zhu X, Ziegler RG, Zonderman AB, Adeyemo A, Ambs S, Cushman M, Faul JD, Hakonarson H, Levin AM, Nathanson KL, Ware EB, Weir DR, Zhao W, Zhi D; Bone Mineral Density in Childhood Study (BMDCS) Group, Arnett DK, Grant SFA, Kardia SLR, Oloapde OI, Rao DC, Rotimi CN, Sale MM, Williams LK, Zemel BS, Becker DM, Borecki IB, Evans MK, Harris TB, Hirschhorn JN, Li Y, Patel SR, Psaty BM, Rotter JI, Wilson JG, Bowden DW, Cupples LA, Haiman CA, Loos RJF, North KE. Ng MCY, et al. PLoS Genet. 2017 Apr 21;13(4):e1006719. doi: 10.1371/journal.pgen.1006719. eCollection 2017 Apr. PLoS Genet. 2017. PMID: 28430825 Free PMC article.
  • Genetic risk factors for BMI and obesity in an ethnically diverse population: results from the population architecture using genomics and epidemiology (PAGE) study.
    Fesinmeyer MD, North KE, Ritchie MD, Lim U, Franceschini N, Wilkens LR, Gross MD, Bůžková P, Glenn K, Quibrera PM, Fernández-Rhodes L, Li Q, Fowke JH, Li R, Carlson CS, Prentice RL, Kuller LH, Manson JE, Matise TC, Cole SA, Chen CT, Howard BV, Kolonel LN, Henderson BE, Monroe KR, Crawford DC, Hindorff LA, Buyske S, Haiman CA, Le Marchand L, Peters U. Fesinmeyer MD, et al. Obesity (Silver Spring). 2013 Apr;21(4):835-46. doi: 10.1002/oby.20268. Obesity (Silver Spring). 2013. PMID: 23712987 Free PMC article.
  • Fine Mapping and Identification of BMI Loci in African Americans.
    Gong J, Schumacher F, Lim U, Hindorff LA, Haessler J, Buyske S, Carlson CS, Rosse S, Bůžková P, Fornage M, Gross M, Pankratz N, Pankow JS, Schreiner PJ, Cooper R, Ehret G, Gu CC, Houston D, Irvin MR, Jackson R, Kuller L, Henderson B, Cheng I, Wilkens L, Leppert M, Lewis CE, Li R, Nguyen KD, Goodloe R, Farber-Eger E, Boston J, Dilks HH, Ritchie MD, Fowke J, Pooler L, Graff M, Fernandez-Rhodes L, Cochrane B, Boerwinkle E, Kooperberg C, Matise TC, Le Marchand L, Crawford DC, Haiman CA, North KE, Peters U. Gong J, et al. Am J Hum Genet. 2013 Oct 3;93(4):661-71. doi: 10.1016/j.ajhg.2013.08.012. Am J Hum Genet. 2013. PMID: 24094743 Free PMC article.
  • Meta-Analysis of Genome-Wide Association Studies Identifies Genetic Risk Factors for Stroke in African Americans.
    Carty CL, Keene KL, Cheng YC, Meschia JF, Chen WM, Nalls M, Bis JC, Kittner SJ, Rich SS, Tajuddin S, Zonderman AB, Evans MK, Langefeld CD, Gottesman R, Mosley TH, Shahar E, Woo D, Yaffe K, Liu Y, Sale MM, Dichgans M, Malik R, Longstreth WT Jr, Mitchell BD, Psaty BM, Kooperberg C, Reiner A, Worrall BB, Fornage M; COMPASS and METASTROKE Consortia. Carty CL, et al. Stroke. 2015 Aug;46(8):2063-8. doi: 10.1161/STROKEAHA.115.009044. Epub 2015 Jun 18. Stroke. 2015. PMID: 26089329 Free PMC article.
  • Genome-Wide Association Study Identifies African-Specific Susceptibility Loci in African Americans With Inflammatory Bowel Disease.
    Brant SR, Okou DT, Simpson CL, Cutler DJ, Haritunians T, Bradfield JP, Chopra P, Prince J, Begum F, Kumar A, Huang C, Venkateswaran S, Datta LW, Wei Z, Thomas K, Herrinton LJ, Klapproth JA, Quiros AJ, Seminerio J, Liu Z, Alexander JS, Baldassano RN, Dudley-Brown S, Cross RK, Dassopoulos T, Denson LA, Dhere TA, Dryden GW, Hanson JS, Hou JK, Hussain SZ, Hyams JS, Isaacs KL, Kader H, Kappelman MD, Katz J, Kellermayer R, Kirschner BS, Kuemmerle JF, Kwon JH, Lazarev M, Li E, Mack D, Mannon P, Moulton DE, Newberry RD, Osuntokun BO, Patel AS, Saeed SA, Targan SR, Valentine JF, Wang MH, Zonca M, Rioux JD, Duerr RH, Silverberg MS, Cho JH, Hakonarson H, Zwick ME, McGovern DP, Kugathasan S. Brant SR, et al. Gastroenterology. 2017 Jan;152(1):206-217.e2. doi: 10.1053/j.gastro.2016.09.032. Epub 2016 Sep 28. Gastroenterology. 2017. PMID: 27693347 Free PMC article. Clinical Trial.
See all similar articles

Cited by 114 articles

See all "Cited by" articles

References

    1. Flegal KM, Carroll MD, Kit BK, Ogden CL. Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999–2010. Jama. 2012;307:491–7. - PubMed
    1. Bradfield JP, et al. A genome-wide association meta-analysis identifies new childhood obesity loci. Nat Genet. 2012 - PMC - PubMed
    1. Thorleifsson G, et al. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat Genet. 2009;41:18–24. - PubMed
    1. Frayling TM, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007;316:889–94. - PMC - PubMed
    1. Scuteri A, et al. Genome-Wide Association Scan Shows Genetic Variants in the FTO Gene Are Associated with Obesity-Related Traits. PLoS Genet. 2007;3:e115. - PMC - PubMed

Publication types

Grant support

Feedback