05300nas a2201225 4500008004100000022001400041245016600055210006900221260001600290300001300306490000700319520181200326653001402138653001002152653000902162653002202171653002002193653004002213653001102253653003402264653001102298653000902309653001602318653002402334653002002358653001602378100002202394700001502416700002502431700002302456700002102479700002602500700002502526700002102551700001802572700002302590700002402613700002302637700001902660700001602679700001402695700002902709700001802738700002202756700001402778700002002792700002302812700001802835700002402853700002302877700001902900700003102919700002702950700002602977700001803003700001603021700002003037700002203057700001803079700001603097700001903113700002103132700002103153700002903174700002003203700002103223700002403244700002203268700001503290700002203305700002303327700001803350700002203368700002003390700002103410700002403431700002203455700001903477700002503496700002103521700002103542700002503563700001903588700002103607700002203628700002403650700002203674700001903696700002303715700002103738700002003759700001703779700002203796700002103818700002303839700002103862700001903883700002003902700002103922700002003943710003003963710002103993710002404014856003604038 2014 eng d a1460-208300aGene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of European descent confirm known loci and reveal several novel associations.0 aGenecentric metaanalyses for central adiposity traits in up to 5 c2014 May 01 a2498-5100 v233 a
Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are associated with adverse cardiovascular events, type 2 diabetes and cancer independent of body mass index (BMI). WC and WHR are highly heritable with multiple susceptibility loci identified to date. We assessed the association between SNPs and BMI-adjusted WC and WHR and unadjusted WC in up to 57 412 individuals of European descent from 22 cohorts collaborating with the NHLBI's Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 20-80 years. Study participants were genotyped using the ITMAT/Broad/CARE array, which includes ∼50 000 cosmopolitan tagged SNPs across ∼2100 cardiovascular-related genes. Each trait was modeled as a function of age, study site and principal components to control for population stratification, and we conducted a fixed-effects meta-analysis. No new loci for WC were observed. For WHR analyses, three novel loci were significantly associated (P < 2.4 × 10(-6)). Previously unreported rs2811337-G near TMCC1 was associated with increased WHR (β ± SE, 0.048 ± 0.008, P = 7.7 × 10(-9)) as was rs7302703-G in HOXC10 (β = 0.044 ± 0.008, P = 2.9 × 10(-7)) and rs936108-C in PEMT (β = 0.035 ± 0.007, P = 1.9 × 10(-6)). Sex-stratified analyses revealed two additional novel signals among females only, rs12076073-A in SHC1 (β = 0.10 ± 0.02, P = 1.9 × 10(-6)) and rs1037575-A in ATBDB4 (β = 0.046 ± 0.01, P = 2.2 × 10(-6)), supporting an already established sexual dimorphism of central adiposity-related genetic variants. Functional analysis using ENCODE and eQTL databases revealed that several of these loci are in regulatory regions or regions with differential expression in adipose tissue.
10aAdiposity10aAdult10aAged10aAged, 80 and over10aBody Mass Index10aEuropean Continental Ancestry Group10aFemale10aGenome-Wide Association Study10aHumans10aMale10aMiddle Aged10aWaist Circumference10aWaist-Hip Ratio10aYoung Adult1 aYoneyama, Sachiko1 aGuo, Yiran1 aLanktree, Matthew, B1 aBarnes, Michael, R1 aElbers, Clara, C1 aKarczewski, Konrad, J1 aPadmanabhan, Sandosh1 aBauer, Florianne1 aBaumert, Jens1 aBeitelshees, Amber1 aBerenson, Gerald, S1 aBoer, Jolanda, M A1 aBurke, Gregory1 aCade, Brian1 aChen, Wei1 aCooper-Dehoff, Rhonda, M1 aGaunt, Tom, R1 aGieger, Christian1 aGong, Yan1 aGorski, Mathias1 aHeard-Costa, Nancy1 aJohnson, Toby1 aLamonte, Michael, J1 aMcDonough, Caitrin1 aMonda, Keri, L1 aOnland-Moret, Charlotte, N1 aNelson, Christopher, P1 aO'Connell, Jeffrey, R1 aOrdovas, Jose1 aPeter, Inga1 aPeters, Annette1 aShaffer, Jonathan1 aShen, Haiqinq1 aSmith, Erin1 aSpeilotes, Liz1 aThomas, Fridtjof1 aThorand, Barbara1 aVerschuren, W, M Monique1 aAnand, Sonia, S1 aDominiczak, Anna1 aDavidson, Karina, W1 aHegele, Robert, A1 aHeid, Iris1 aHofker, Marten, H1 aHuggins, Gordon, S1 aIllig, Thomas1 aJohnson, Julie, A1 aKirkland, Susan1 aKönig, Wolfgang1 aLangaee, Taimour, Y1 aMcCaffery, Jeanne1 aMelander, Olle1 aMitchell, Braxton, D1 aMunroe, Patricia1 aMurray, Sarah, S1 aPapanicolaou, George1 aRedline, Susan1 aReilly, Muredach1 aSamani, Nilesh, J1 aSchork, Nicholas, J1 aSchouw, Yvonne, T1 aShimbo, Daichi1 aShuldiner, Alan, R1 aTobin, Martin, D1 aWijmenga, Cisca1 aYusuf, Salim1 aHakonarson, Hakon1 aLange, Leslie, A1 aDemerath, Ellen, W1 aFox, Caroline, S1 aNorth, Kari, E1 aReiner, Alex, P1 aKeating, Brendan1 aTaylor, Kira, C1 aLook AHEAD Research Group1 aGIANT Consortium1 aCARe IBC Consortium uhttps://chs-nhlbi.org/node/6368