Medical Genomics Center, National Center for Global Health and Medicine, Tokyo, 162-8655, Japan.
Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, 162-8655, Japan.
Nat Commun. 2018 Nov 28;9(1):5052. doi: 10.1038/s41467-018-07345-0.
Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP (max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize within the same linkage disequilibrium block despite the significantly discordant effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect-sizes is 0.898 and 0.851 for systolic and diastolic BP, respectively. Some of the ancestry-specific association signals are also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP.
血压（BP）是心血管疾病的主要风险因素，已知有 200 多个与 BP 相关的遗传位点。在这里，我们主要在东亚人群中进行了 BP 的多阶段全基因组关联研究（最大 N=289038），并在东亚和欧洲人群中进行了荟萃分析。我们报告了 19 个新的遗传位点和与祖先相关的 BP 变体，符合共同的祖先特异性变体关联模型。在 10 个独特的位点上，尽管在不同种族群体中，代表共享变体的效应存在显著差异，但不同的非罕见与祖先相关的变体仍在同一连锁不平衡块内共同定位。因果变体效应大小的全基因组跨种族相关性分别为收缩压和舒张压的 0.898 和 0.851。一些与祖先相关的关联信号也受到选择清除的影响。我们的研究结果为共同的祖先特异性变体和自然选择在 BP 等复杂特征的种族差异中的作用提供了新的证据。
