Robinson Matthew R, Hemani Gibran, Medina-Gomez Carolina, Mezzavilla Massimo, Esko Tonu, Shakhbazov Konstantin, Powell Joseph E, Vinkhuyzen Anna, Berndt Sonja I, Gustafsson Stefan, Justice Anne E, Kahali Bratati, Locke Adam E, Pers Tune H, Vedantam Sailaja, Wood Andrew R, van Rheenen Wouter, Andreassen Ole A, Gasparini Paolo, Metspalu Andres, Berg Leonard H van den, Veldink Jan H, Rivadeneira Fernando, Werge Thomas M, Abecasis Goncalo R, Boomsma Dorret I, Chasman Daniel I, de Geus Eco J C, Frayling Timothy M, Hirschhorn Joel N, Hottenga Jouke Jan, Ingelsson Erik, Loos Ruth J F, Magnusson Patrik K E, Martin Nicholas G, Montgomery Grant W, North Kari E, Pedersen Nancy L, Spector Timothy D, Speliotes Elizabeth K, Goddard Michael E, Yang Jian, Visscher Peter M
Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
Nat Genet. 2015 Nov;47(11):1357-62. doi: 10.1038/ng.3401. Epub 2015 Sep 14.
Across-nation differences in the mean values for complex traits are common, but the reasons for these differences are unknown. Here we find that many independent loci contribute to population genetic differences in height and body mass index (BMI) in 9,416 individuals across 14 European countries. Using discovery data on over 250,000 individuals and unbiased effect size estimates from 17,500 sibling pairs, we estimate that 24% (95% credible interval (CI) = 9%, 41%) and 8% (95% CI = 4%, 16%) of the captured additive genetic variance for height and BMI, respectively, reflect population genetic differences. Population genetic divergence differed significantly from that in a null model (height, P < 3.94 × 10(-8); BMI, P < 5.95 × 10(-4)), and we find an among-population genetic correlation for tall and slender individuals (r = -0.80, 95% CI = -0.95, -0.60), consistent with correlated selection for both phenotypes. Observed differences in height among populations reflected the predicted genetic means (r = 0.51; P < 0.001), but environmental differences across Europe masked genetic differentiation for BMI (P < 0.58).
复杂性状均值的跨国差异很常见，但这些差异的原因尚不清楚。在这里，我们发现许多独立基因座对14个欧洲国家的9416名个体的身高和体重指数（BMI）的群体遗传差异有贡献。利用超过250,000名个体的发现数据和来自17,500对同胞对的无偏效应大小估计，我们估计身高和BMI的捕获加性遗传方差分别有24%（95%可信区间（CI）= 9%，41%）和8%（95% CI = 4%，16%）反映了群体遗传差异。群体遗传分化与零模型中的分化显著不同（身高，P < 3.94 × 10(-8)；BMI，P < 5.95 × 10(-4)），并且我们发现高个子和苗条个体之间存在群体间遗传相关性（r = -0.80，95% CI = -0.95，-0.60），这与两种表型的相关选择一致。群体间观察到的身高差异反映了预测的遗传均值（r = 0.51；P < 0.001），但欧洲各地的环境差异掩盖了BMI的遗传分化（P < 0.58）。
