Obesity is a worldwide epidemic, with major health and economic costs. Here we estimate heritability for body mass index (BMI) in 172,000 sibling pairs and 150,832 unrelated individuals and explore the contribution of genotype-covariate interaction effects at common SNP loci. We find evidence for genotype-age interaction (likelihood ratio test (LRT) = 73.58, degrees of freedom (df) = 1, P = 4.83 × 10^-18), which contributed 8.1% (1.4% s.e.) to BMI variation. Across eight self-reported lifestyle factors, including diet and exercise, we find genotype-environment interaction only for smoking behavior (LRT = 19.70, P = 5.03 × 10^-5 and LRT = 30.80, P = 1.42 × 10^-8), which contributed 4.0% (0.8% s.e.) to BMI variation. Bayesian association analysis suggests that BMI is highly polygenic, with 75% of the SNP heritability attributable to loci that each explain <0.01% of the phenotypic variance. Our findings imply that substantially larger sample sizes across ages and lifestyles are required to understand the full genetic architecture of BMI.

中文翻译：

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基因型-协变量相互作用的影响和成年体重指数的遗传性。

肥胖症是一种全球流行病，具有重大的健康和经济成本。在这里，我们估计了172,000个同胞对和150,832个无关个体的体重指数（BMI）的遗传力，并探讨了基因型-协变量相互作用对常见SNP位点的影响。我们发现了基因型-年龄相互作用的证据（似然比检验（LRT）= 73.58，自由度（df）= 1，P = 4.83×10 ^-18），其对BMI变异的贡献为8.1％（1.4％se）。在包括饮食和运动在内的八个自我报告的生活方式因素中，我们发现基因型与环境之间的相互作用仅针对吸烟行为（LRT = 19.70，P = 5.03×10 ^-5和LRT = 30.80，P = 1.42×10 ^-8），这为BMI变化贡献了4.0％（即0.8％se）。贝叶斯关联分析表明，BMI具有高度的多基因性，其中SNP遗传力的75％可归因于基因座，每个基因座解释了<0.01％的表型变异。我们的发现表明，要了解BMI的完整遗传结构，就需要跨年龄和生活方式的更大样本量。