06047nas a2201393 4500008004100000022001400041245010400055210006900159260000900228300001300237490000600250520209200256653001402348653003902362653002602401653004002427653001102467653001702478653003402495653001102529653000902540653001202549653003602561653002002597100001802617700001902635700002002654700001802674700002302692700001902715700002402734700002102758700002202779700001502801700002802816700002502844700001602869700002202885700002202907700002302929700001802952700001202970700002802982700001803010700001503028700002403043700002403067700002803091700001903119700001703138700002503155700001603180700002203196700001903218700002003237700002303257700002203280700002803302700001703330700002003347700002303367700001503390700001703405700002003422700002103442700001803463700002203481700002303503700002303526700003103549700002203580700002003602700001703622700002803639700001403667700002403681700002403705700002203729700002103751700001803772700001403790700003203804700002503836700002403861700001703885700002403902700002103926700002103947700002803968700002203996700002004018700002104038700002104059700002704080700002204107700002304129700002104152700002404173700001704197700002404214700002304238700002204261700002104283700002504304700002304329700002204352700001904374700002204393700002104415700002804436700002304464700001804487700002204505700002504527700002504552700001904577700002104596856003604617 2013 eng d a1553-740400aGenome-wide association of body fat distribution in African ancestry populations suggests new loci.0 aGenomewide association of body fat distribution in African ances c2013 ae10036810 v93 a
Central obesity, measured by waist circumference (WC) or waist-hip ratio (WHR), is a marker of body fat distribution. Although obesity disproportionately affects minority populations, few studies have conducted genome-wide association study (GWAS) of fat distribution among those of predominantly African ancestry (AA). We performed GWAS of WC and WHR, adjusted and unadjusted for BMI, in up to 33,591 and 27,350 AA individuals, respectively. We identified loci associated with fat distribution in AA individuals using meta-analyses of GWA results for WC and WHR (stage 1). Overall, 25 SNPs with single genomic control (GC)-corrected p-values<5.0 × 10(-6) were followed-up (stage 2) in AA with WC and with WHR. Additionally, we interrogated genomic regions of previously identified European ancestry (EA) WHR loci among AA. In joint analysis of association results including both Stage 1 and 2 cohorts, 2 SNPs demonstrated association, rs2075064 at LHX2, p = 2.24×10(-8) for WC-adjusted-for-BMI, and rs6931262 at RREB1, p = 2.48×10(-8) for WHR-adjusted-for-BMI. However, neither signal was genome-wide significant after double GC-correction (LHX2: p = 6.5 × 10(-8); RREB1: p = 5.7 × 10(-8)). Six of fourteen previously reported loci for waist in EA populations were significant (p<0.05 divided by the number of independent SNPs within the region) in AA studied here (TBX15-WARS2, GRB14, ADAMTS9, LY86, RSPO3, ITPR2-SSPN). Further, we observed associations with metabolic traits: rs13389219 at GRB14 associated with HDL-cholesterol, triglycerides, and fasting insulin, and rs13060013 at ADAMTS9 with HDL-cholesterol and fasting insulin. Finally, we observed nominal evidence for sexual dimorphism, with stronger results in AA women at the GRB14 locus (p for interaction = 0.02). In conclusion, we identified two suggestive loci associated with fat distribution in AA populations in addition to confirming 6 loci previously identified in populations of EA. These findings reinforce the concept that there are fat distribution loci that are independent of generalized adiposity.
10aAdiposity10aAfrican Continental Ancestry Group10aBody Fat Distribution10aEuropean Continental Ancestry Group10aFemale10aGenetic Loci10aGenome-Wide Association Study10aHumans10aMale10aObesity10aPolymorphism, Single Nucleotide10aWaist-Hip Ratio1 aLiu, Ching-Ti1 aMonda, Keri, L1 aTaylor, Kira, C1 aLange, Leslie1 aDemerath, Ellen, W1 aPalmas, Walter1 aWojczynski, Mary, K1 aEllis, Jaclyn, C1 aVitolins, Mara, Z1 aLiu, Simin1 aPapanicolaou, George, J1 aIrvin, Marguerite, R1 aXue, Luting1 aGriffin, Paula, J1 aNalls, Michael, A1 aAdeyemo, Adebowale1 aLiu, Jiankang1 aLi, Guo1 aRuiz-Narvaez, Edward, A1 aChen, Wei-Min1 aChen, Fang1 aHenderson, Brian, E1 aMillikan, Robert, C1 aAmbrosone, Christine, B1 aStrom, Sara, S1 aGuo, Xiuqing1 aAndrews, Jeanette, S1 aSun, Yan, V1 aMosley, Thomas, H1 aYanek, Lisa, R1 aShriner, Daniel1 aHaritunians, Talin1 aRotter, Jerome, I1 aSpeliotes, Elizabeth, K1 aSmith, Megan1 aRosenberg, Lynn1 aMychaleckyj, Josyf1 aNayak, Uma1 aSpruill, Ida1 aGarvey, Timothy1 aPettaway, Curtis1 aNyante, Sarah1 aBandera, Elisa, V1 aBritton, Angela, F1 aZonderman, Alan, B1 aRasmussen-Torvik, Laura, J1 aChen, Yii-Der Ida1 aDing, Jingzhong1 aLohman, Kurt1 aKritchevsky, Stephen, B1 aZhao, Wei1 aPeyser, Patricia, A1 aKardia, Sharon, L R1 aKabagambe, Edmond1 aBroeckel, Ulrich1 aChen, Guanjie1 aZhou, Jie1 aWassertheil-Smoller, Sylvia1 aNeuhouser, Marian, L1 aRampersaud, Evadnie1 aPsaty, Bruce1 aKooperberg, Charles1 aManson, JoAnn, E1 aKuller, Lewis, H1 aOchs-Balcom, Heather, M1 aJohnson, Karen, C1 aSucheston, Lara1 aOrdovas, Jose, M1 aPalmer, Julie, R1 aHaiman, Christopher, A1 aMcKnight, Barbara1 aHoward, Barbara, V1 aBecker, Diane, M1 aBielak, Lawrence, F1 aLiu, Yongmei1 aAllison, Matthew, A1 aGrant, Struan, F A1 aBurke, Gregory, L1 aPatel, Sanjay, R1 aSchreiner, Pamela, J1 aBorecki, Ingrid, B1 aEvans, Michele, K1 aTaylor, Herman1 aSale, Michèle, M1 aHoward, Virginia1 aCarlson, Christopher, S1 aRotimi, Charles, N1 aCushman, Mary1 aHarris, Tamara, B1 aReiner, Alexander, P1 aCupples, Adrienne, L1 aNorth, Kari, E1 aFox, Caroline, S uhttps://chs-nhlbi.org/node/628705814nas a2201345 4500008004100000022001400041245014200055210006900197260001300266300001300279490000700292520193700299653002202236653003002258653003402288653002002322653001802342653001102360653002802371653002902399653003602428653004202464100001902506700002002525700001902545700001402564700001802578700001702596700001802613700002602631700001902657700002202676700002002698700003102718700002302749700002102772700001602793700001302809700002102822700001802843700001702861700002402878700002302902700001802925700002402943700002602967700001902993700002303012700002003035700002303055700002603078700001503104700002203119700002203141700001903163700002203182700001903204700001603223700001803239700002103257700002103278700002303299700001803322700001803340700002303358700002203381700002503403700002303428700001903451700001903470700002503489700002403514700002203538700001803560700001703578700001903595700001403614700002403628700001603652700002503668700002403693700002003717700001603737700001503753700002103768700002103789700002503810700002203835700002003857700002103877700002003898700001703918700002003935700002303955700002403978700002404002700002004026700002004046700002204066700002204088700002104110700002004131700002104151700002204172700002204194700001504216700002304231700002204254710002004276710002204296710002304318710002204341710006904363856003604432 2014 eng d a1553-740400aMeta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes.0 aMetaanalysis of genomewide association studies in African Americ c2014 Aug ae10045170 v103 aType 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)
10aAfrican Americans10aDiabetes Mellitus, Type 210aGenome-Wide Association Study10aHLA-B27 Antigen10aHMGA2 Protein10aHumans10aKCNQ1 Potassium Channel10aMutant Chimeric Proteins10aPolymorphism, Single Nucleotide10aTranscription Factor 7-Like 2 Protein1 aC Y Ng, Maggie1 aShriner, Daniel1 aChen, Brian, H1 aLi, Jiang1 aChen, Wei-Min1 aGuo, Xiuqing1 aLiu, Jiankang1 aBielinski, Suzette, J1 aYanek, Lisa, R1 aNalls, Michael, A1 aComeau, Mary, E1 aRasmussen-Torvik, Laura, J1 aJensen, Richard, A1 aEvans, Daniel, S1 aSun, Yan, V1 aAn, Ping1 aPatel, Sanjay, R1 aLu, Yingchang1 aLong, Jirong1 aArmstrong, Loren, L1 aWagenknecht, Lynne1 aYang, Lingyao1 aSnively, Beverly, M1 aPalmer, Nicholette, D1 aMudgal, Poorva1 aLangefeld, Carl, D1 aKeene, Keith, L1 aFreedman, Barry, I1 aMychaleckyj, Josyf, C1 aNayak, Uma1 aRaffel, Leslie, J1 aGoodarzi, Mark, O1 aChen, Y-D, Ida1 aTaylor, Herman, A1 aCorrea, Adolfo1 aSims, Mario1 aCouper, David1 aPankow, James, S1 aBoerwinkle, Eric1 aAdeyemo, Adebowale1 aDoumatey, Ayo1 aChen, Guanjie1 aMathias, Rasika, A1 aVaidya, Dhananjay1 aSingleton, Andrew, B1 aZonderman, Alan, B1 aIgo, Robert, P1 aSedor, John, R1 aKabagambe, Edmond, K1 aSiscovick, David, S1 aMcKnight, Barbara1 aRice, Kenneth1 aLiu, Yongmei1 aHsueh, Wen-Chi1 aZhao, Wei1 aBielak, Lawrence, F1 aKraja, Aldi1 aProvince, Michael, A1 aBottinger, Erwin, P1 aGottesman, Omri1 aCai, Qiuyin1 aZheng, Wei1 aBlot, William, J1 aLowe, William, L1 aPacheco, Jennifer, A1 aCrawford, Dana, C1 aGrundberg, Elin1 aRich, Stephen, S1 aHayes, Geoffrey1 aShu, Xiao-Ou1 aLoos, Ruth, J F1 aBorecki, Ingrid, B1 aPeyser, Patricia, A1 aCummings, Steven, R1 aPsaty, Bruce, M1 aFornage, Myriam1 aIyengar, Sudha, K1 aEvans, Michele, K1 aBecker, Diane, M1 aKao, Linda, W H1 aWilson, James, G1 aRotter, Jerome, I1 aSale, Michèle, M1 aLiu, Simin1 aRotimi, Charles, N1 aBowden, Donald, W1 aFIND Consortium1 aeMERGE Consortium1 aDIAGRAM Consortium1 aMuTHER Consortium1 aMEta-analysis of type 2 DIabetes in African Americans Consortium uhttps://chs-nhlbi.org/node/6585