Replication and extension of genome-wide association study results for obesity in 4923 adults from northern Sweden

被引：192

作者：

Renstrom, Frida ^{[1
]}

Payne, Felicity ^{[2
]}

Nordstrom, Anna ^{[3
,4
]}

Brito, Ema C. ^{[1
]}

Rolandsson, Olov ^{[5
]}

Hallmans, Goeran ^{[6
]}

Barroso, Ines ^{[2
]}

Nordstrom, Peter ^{[3
,7
]}

Franks, Paul W. ^{[1
]}

机构：

[1] Umea Univ Hosp, Genet Epidemiol & Clin Res Grp, Dept Publ Hlth & Clin Med, Med Sect, S-90187 Umea, Sweden

[2] Wellcome Trust Sanger Inst, Metab Dis Grp, Cambridge CB10 1SA, England

[3] Umea Univ, Dept Surg & Perioperat Sci, Sect Sports Med, S-90185 Umea, Sweden

[4] Umea Univ, Dept Community Med & Rehabil, Sect Rehabil Med, S-90185 Umea, Sweden

[5] Umea Univ, Dept Publ Hlth & Clin Med, Sect Family Med, S-90185 Umea, Sweden

[6] Umea Univ, Dept Publ Hlth & Clin Med, Sect Nutrit Res, S-90185 Umea, Sweden

[7] Umea Univ Hosp, Dept Community Med & Rehabil, Geriatr Med Sect, S-90187 Umea, Sweden

来源：

HUMAN MOLECULAR GENETICS | 2009年 / 18卷 / 08期

基金：

英国惠康基金;

关键词：

FAT MASS; VARIANTS; RISK; MC4R; GENE;

D O I：

10.1093/hmg/ddp041

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Recent genome-wide association studies (GWAS) have identified multiple risk loci for common obesity (FTO, MC4R, TMEM18, GNPDA2, SH2B1, KCTD15, MTCH2, NEGR1 and PCSK1). Here we extend those studies by examining associations with adiposity and type 2 diabetes in Swedish adults. The nine single nucleotide polymorphisms (SNPs) were genotyped in 3885 non-diabetic and 1038 diabetic individuals with available measures of height, weight and body mass index (BMI). Adipose mass and distribution were objectively assessed using dual-energy X-ray absorptiometry in a sub-group of non-diabetics (n = 2206). In models with adipose mass traits, BMI or obesity as outcomes, the most strongly associated SNP was FTO rs1121980 (P < 0.001). Five other SNPs (SH2B1 rs7498665, MTCH2 rs4752856, MC4R rs17782313, NEGR1 rs2815752 and GNPDA2 rs10938397) were significantly associated with obesity. To summarize the overall genetic burden, a weighted risk score comprising a subset of SNPs was constructed; those in the top quintile of the score were heavier (+2.6 kg) and had more total (+2.4 kg), gynoid (+191 g) and abdominal (+136 g) adipose tissue than those in the lowest quintile (all P < 0.001). The genetic burden score significantly increased diabetes risk, with those in the highest quintile (n = 193/594 cases/controls) being at 1.55-fold (95% CI 1.21-1.99; P < 0.0001) greater risk of type 2 diabetes than those in the lowest quintile (n = 130/655 cases/controls). In summary, we have statistically replicated six of the previously associated obese-risk loci and our results suggest that the weight-inducing effects of these variants are explained largely by increased adipose accumulation.

引用

页码：1489 / 1496

页数：8

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