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基于全基因组关联研究的荟萃分析鉴定了与东亚人群血压变化相关的常见变异。

Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians.

机构信息

Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.

出版信息

Nat Genet. 2011 Jun;43(6):531-8. doi: 10.1038/ng.834. Epub 2011 May 15.

Abstract

We conducted a meta-analysis of genome-wide association studies of systolic (SBP) and diastolic (DBP) blood pressure in 19,608 subjects of east Asian ancestry from the AGEN-BP consortium followed up with de novo genotyping (n = 10,518) and further replication (n = 20,247) in east Asian samples. We identified genome-wide significant (P < 5 × 10(-8)) associations with SBP or DBP, which included variants at four new loci (ST7L-CAPZA1, FIGN-GRB14, ENPEP and NPR3) and a newly discovered variant near TBX3. Among the five newly discovered variants, we obtained significant replication in the independent samples for all of these loci except NPR3. We also confirmed seven loci previously identified in populations of European descent. Moreover, at 12q24.13 near ALDH2, we observed strong association signals (P = 7.9 × 10(-31) and P = 1.3 × 10(-35) for SBP and DBP, respectively) with ethnic specificity. These findings provide new insights into blood pressure regulation and potential targets for intervention.

摘要

我们对东亚裔人群中的 19608 名个体进行了一项与收缩压(SBP)和舒张压(DBP)相关的全基因组关联研究,这些个体来自 AGEN-BP 联合会,并进行了从头基因分型(n=10518)和进一步的复制(n=20247)。我们在东亚人群样本中发现了与 SBP 或 DBP 相关的全基因组显著关联(P<5×10(-8)),这些关联包括四个新的位点(ST7L-CAPZA1、FIGN-GRB14、ENPEP 和 NPR3)和一个在 TBX3 附近新发现的变异。在五个新发现的变异中,除了 NPR3 之外,我们在独立样本中都获得了显著的复制。我们还确认了在欧洲血统人群中先前确定的七个位点。此外,在 12q24.13 附近的 ALDH2 附近,我们观察到与种族特异性强烈相关的关联信号(SBP 和 DBP 的 P 值分别为 7.9×10(-31)和 1.3×10(-35))。这些发现为血压调节和潜在的干预靶点提供了新的见解。

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