Population genetic differentiation of height and body mass index across Europe.
Population genetic differentiation of height and body mass index across Europe.
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DOI：
10.1038/ng.3401
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发表时间：
2015-11
期刊：
影响因子：
30.8
通讯作者：
Visscher PM
中科院分区：
文献类型：
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作者：
Robinson MR;Hemani G;Medina-Gomez C;Mezzavilla M;Esko T;Shakhbazov K;Powell JE;Vinkhuyzen A;Berndt SI;Gustafsson S;Justice AE;Kahali B;Locke AE;Pers TH;Vedantam S;Wood AR;van Rheenen W;Andreassen OA;Gasparini P;Metspalu A;Berg LH;Veldink JH;Rivadeneira F;Werge TM;Abecasis GR;Boomsma DI;Chasman DI;de Geus EJ;Frayling TM;Hirschhorn JN;Hottenga JJ;Ingelsson E;Loos RJ;Magnusson PK;Martin NG;Montgomery GW;North KE;Pedersen NL;Spector TD;Speliotes EK;Goddard ME;Yang J;Visscher PM
肥胖和身材等复杂性状的平均值在全国范围内存在差异是很常见的，但这些差异的原因尚不清楚。在这里，我们发现证据表明，在14个欧洲国家的9,416名个体样本中，许多独立的小效应基因座联合收割机结合在一起，造成了身高和体重指数（BMI）的群体遗传差异。使用超过250，000个个体的发现数据和来自17，500个同胞对的效应大小的无偏估计，我们估计在欧洲范围内捕获的身高和BMI的加性遗传方差的24%（95%CI：9%，41%）和8%（95%CI：4%，16%）归因于非群体遗传差异。群体遗传分化与零模型下的预期差异显著（身高P <3.94e-08，体重指数P <5.95e-04），我们发现高个子和苗条的民族与人口的遗传相关性（r =-0.80（95%CI：-0.95，-0.60），对比人群中身高和BMI之间没有遗传相关性（r =-0.016，95%CI：-0.041，0.001），这与对身高基因的选择一致，这些基因也可以降低BMI。不同国家的平均身高观察值与预测的身高遗传平均值相关（r = 0.51，P <0.001），因此，在欧洲观察到的身高差异的一部分反映了遗传因素。相反，观察到的平均BMI与遗传估计值无关（P <0.58），这意味着BMI的遗传差异被整个欧洲的环境差异所掩盖。
Across-nation differences in the mean of complex traits such as obesity and stature are common, but the reasons for these differences are not known. Here, we find evidence that many independent loci of small effect combine to create population genetic differences in height and body mass index (BMI) in a sample of 9,416 individuals across 14 European countries. Using discovery data on over 250,000 individuals and unbiased estimates of effect sizes from 17,500 sib pairs, we estimate that 24% (95% CI: 9%, 41%) and 8% (95% CI: 4%, 16%) of the captured additive genetic variance for height and BMI across Europe are attributed to among-population genetic differences. Population genetic divergence differed significantly from that expected under a null model (P <3.94e−08 for height and P<5.95e−04 for BMI), and we find an among-population genetic correlation for tall and slender nations (r = −0.80 (95% CI: −0.95, −0.60), contrasting no genetic correlation between height and BMI within populations (r = −0.016, 95% CI: −0.041, 0.001), consistent with selection on height genes that also act to reduce BMI. Observations of mean height across nations correlated with the predicted genetic means for height (r = 0.51, P<0.001), so that a proportion of observed differences in height within Europe reflect genetic factors. In contrast, observed mean BMI did not correlate with the genetic estimates (P<0.58), implying that genetic differentiation in BMI is masked by environmental differences across Europe.