Susceptibility loci for metabolic syndrome and metabolic components identified in Han Chinese: a multi-stage genome-wide association study.
Susceptibility loci for metabolic syndrome and metabolic components identified in Han Chinese: a multi-stage genome-wide association study.
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DOI：
10.1111/jcmm.13042
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发表时间：
2017-06
影响因子：
5.3
通讯作者：
Lai M
中科院分区：
文献类型：
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作者：
Zhu Y;Zhang D;Zhou D;Li Z;Li Z;Fang L;Yang M;Shan Z;Li H;Chen J;Zhou X;Ye W;Yu S;Li H;Cai L;Liu C;Zhang J;Wang L;Lai Y;Ruan L;Sun Z;Zhang S;Wang H;Liu Y;Xu Y;Ling J;Xu C;Zhang Y;Lv D;Yuan Z;Zhang J;Zhang Y;Shi Y;Lai M
代谢综合征（MetS）是一组代谢紊乱，会增加心血管疾病和糖尿病的风险，其原因是遗传易感性和环境危险因素。为了确定与 MetS 和代谢成分相关的遗传变异，我们进行了全基因组关联研究，然后在来自中国北部、东北和东部的总共 12,720 名参与者中进行了重复研究。在组合分析中，独立于 APOA5 上 rs651821 处的顶级已知信号，我们新发现了 BUD13 上 rs180326 处的次级甘油三酯相关信号（P 组合 = 2.4 × 10−8）。值得注意的是，通过对 APOA5、BUD13 和甘油三酯的基因型和血清水平进行综合分析，我们观察到 BUD13 是除 APOA5 之外的 rs651821 与血清甘油三酯之间关联的另一个潜在介质。 rs671 (ALDH2) 是一种东亚特有的常见变异，被发现与汉族人的 MetS 相关（P 组合 = 9.7 × 10−22）。 rs671 对代谢成分的影响在饮酒者中比在不饮酒者中更为突出。复制的基因座提供了汉族人 MetS 和代谢成分的遗传基础和机制的信息。
Metabolic syndrome (MetS), a cluster of metabolic disturbances that increase the risk for cardiovascular disease and diabetes, was because of genetic susceptibility and environmental risk factors. To identify the genetic variants associated with MetS and metabolic components, we conducted a genome‐wide association study followed by replications in totally 12,720 participants from the north, north‐eastern and eastern China. In combined analyses, independent of the top known signal at rs651821 on APOA5, we newly identified a secondary triglyceride‐associated signal at rs180326 on BUD13 (P combined = 2.4 × 10−8). Notably, by an integrated analysis of the genotypes and the serum levels of APOA5, BUD13 and triglyceride, we observed that BUD13 was another potential mediator, besides APOA5, of the association between rs651821 and serum triglyceride. rs671 (ALDH2), an east Asian‐specific common variant, was found to be associated with MetS (P combined = 9.7 × 10−22) in Han Chinese. The effects of rs671 on metabolic components were more prominent in drinkers than in non‐drinkers. The replicated loci provided information on the genetic basis and mechanisms of MetS and metabolic components in Han Chinese.