全基因组关联研究鉴定心血管疾病的新靶点。

Genome-wide association studies identify new targets in cardiovascular disease.

机构信息

Howard Hughes Medical Institute and Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, USA.

出版信息

Sci Transl Med. 2010 Sep 8;2(48):48ps46. doi: 10.1126/scitranslmed.3001557.

DOI:10.1126/scitranslmed.3001557

PMID:20826839

Abstract

The prevalence of cardiovascular disease (CVD) continues to increase worldwide, highlighting the need for new therapeutic strategies. A recent meta-analysis of genome-wide association studies (GWASs) of over 100,000 individuals published in Nature identified 59 new loci associated with lipid traits; of these, a locus on chromosome 1p13 was most strongly associated with low-density lipoprotein cholesterol (LDL-C) levels. An accompanying study in Nature identified SORT1 as the causal gene at the 1p13 locus and showed that increased expression of sortilin-1 protein in liver was associated with lower LDL-C levels and a reduced risk of myocardial infarction. Together, these studies provide strong validation of the utility of GWASs in identifying biological pathways relevant to CVD pathogenesis and perhaps treatment.

摘要

心血管疾病 (CVD) 的患病率在全球范围内持续上升，凸显了新的治疗策略的必要性。最近在《自然》杂志上发表的一项对超过 10 万人的全基因组关联研究 (GWAS) 的荟萃分析确定了 59 个与脂质特征相关的新基因座；其中，染色体 1p13 上的一个基因座与低密度脂蛋白胆固醇 (LDL-C) 水平的相关性最强。《自然》杂志的一项伴随研究确定 SORT1 为 1p13 基因座的因果基因，并表明肝脏中 sortilin-1 蛋白的表达增加与 LDL-C 水平降低和心肌梗死风险降低有关。这些研究共同为 GWAS 用于识别与 CVD 发病机制相关的生物学途径，甚至治疗方法的有效性提供了有力的验证。