Replication of 6 obesity genes in a meta-analysis of genome-wide association studies from diverse ancestries.
Replication of 6 obesity genes in a meta-analysis of genome-wide association studies from diverse ancestries.
复制标题
不同祖先的全基因组关联研究荟萃分析中 6 个肥胖基因的复制
DOI：
10.1371/journal.pone.0096149
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Deng HW
中科院分区：
文献类型：
--
作者：
Tan LJ;Zhu H;He H;Wu KH;Li J;Chen XD;Zhang JG;Shen H;Tian Q;Krousel-Wood M;Papasian CJ;Bouchard C;Pérusse L;Deng HW
Obesity is a major public health problem with a significant genetic component. Multiple DNA polymorphisms/genes have been shown to be strongly associated with obesity, typically in populations of European descent. The aim of this study was to verify the extent to which 6 confirmed obesity genes (FTO, CTNNBL1, ADRB2, LEPR, PPARG and UCP2 genes) could be replicated in 8 different samples (n = 11,161) and to explore whether the same genes contribute to obesity-susceptibility in populations of different ancestries (five Caucasian, one Chinese, one African-American and one Hispanic population). GWAS-based data sets with 1000 G imputed variants were tested for association with obesity phenotypes individually in each population, and subsequently combined in a meta-analysis. Multiple variants at the FTO locus showed significant associations with BMI, fat mass (FM) and percentage of body fat (PBF) in meta-analysis. The strongest association was detected at rs7185735 (P-value = 1.01×10−7 for BMI, 1.80×10−6 for FM, and 5.29×10−4 for PBF). Variants at the CTNNBL1, LEPR and PPARG loci demonstrated nominal association with obesity phenotypes (meta-analysis P-values ranging from 1.15×10−3 to 4.94×10−2). There was no evidence of association with variants at ADRB2 and UCP2 genes. When stratified by sex and ethnicity, FTO variants showed sex-specific and ethnic-specific effects on obesity traits. Thus, it is likely that FTO has an important role in the sex- and ethnic-specific risk of obesity. Our data confirmed the role of FTO, CTNNBL1, LEPR and PPARG in obesity predisposition. These findings enhanced our knowledge of genetic associations between these genes and obesity-related phenotypes, and provided further justification for pursuing functional studies of these genes in the pathophysiology of obesity. Sex and ethnic differences in genetic susceptibility across populations of diverse ancestries may contribute to a more targeted prevention and customized treatment of obesity.
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影响因子：
7.7
作者：
Adeyemo A;Chen G;Zhou J;Shriner D;Doumatey A;Huang H;Rotimi C
通讯作者：
Rotimi C
影响因子：
4.5
作者：
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
通讯作者：
North KE
影响因子：
8.2
作者：
Dalgaard, LT;Pedersen, O
通讯作者：
Pedersen, O
影响因子：
3.5
作者：
Liu, Yong-Jun;Liu, Xiao-Gang;Deng, Hong-Wen
通讯作者：
Deng, Hong-Wen
影响因子：
4.9
作者：
Dorajoo, R.;Blakemore, A. I. F.;Tai, E-S
通讯作者：
Tai, E-S