Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
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DOI：
10.1038/ncomms14977
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发表时间：
2017-04-26
影响因子：
16.6
通讯作者：
Cupples, L. Adrienne
中科院分区：
文献类型：
--
作者：
Justice, Anne E.;Winkler, Thomas W.;Cupples, L. Adrienne
在研究遗传对肥胖相关性状的影响时，很少有全基因组关联研究（GWAS）考虑到环境暴露（如吸烟）可能影响整体性状变异。在这里，我们使用来自51,080名当前吸烟者和190,178名非吸烟者（87%的欧洲血统）的GWAS数据来确定影响BMI和中心性肥胖的基因位点，测量腰围和腰臀比，均经BMI调整。我们确定了23个新的遗传位点，其中9个位点具有令人信服的证据表明基因-吸烟相互作用（GxSMK）影响肥胖相关性状。我们在一个独立的研究样本中显示了所有已确定的基因座的一致的效应方向和18个新基因座和5个相互作用基因座的显著性。这些基因座突出了新的生物学功能，包括对氧化应激的反应、成瘾行为和调节功能，强调了在遗传分析中考虑环境的重要性。我们的研究结果表明，吸烟可能会改变整体肥胖和体脂分布的遗传易感性。
Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.