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Nature Com:让脂质更健康的一个遗传变异体

摘要 : 英国布里斯托尔大学等处的研究人员报告了一个罕见的、高影响力遗传变异体,它与血浆中实质性较低的甘油三酯水平有关。血浆甘油三酯水平是心血管病的一个非常明确的风险因素。这个低频率、高影响力变异体是利用对大数量人群所做的全基因组测序识别出的同类变异体中的第一个。相关文章发表于2014年9月16日的《Nature Communications》杂志上。
Nature Com:让脂质更健康的一个遗传变异体

虽然遗传因素已知在决定一个人患心血管病的风险中起重要作用,但迄今所发现的大多数因素都比较普遍,只能对患这种疾病的风险之差异的少部分做出解释。人们希望,全基因组、大数量人群研究将能识别出对疾病风险有更大影响的不太普遍的变异体。

来自UK10K Consortium的Nicole Soranzo及同事发现,英国人口中大约0.25%(约16万人)可能携带APOC3基因的一个版本,他们发现该版本与较低水平的血浆甘油三酯有关。他们还报告说,该变异体与较低水平的“密度非常低的脂蛋白”(被称为“坏胆固醇”)和较高水平的“高密度脂蛋白”(被称为“好胆固醇”)有关。这些变化预计会导致患心血管病的总体风险较低。

原文摘要:

A rare variant in ​APOC3 is associated with plasma triglyceride and VLDL levels in Europeans

Nicholas J. Timpson, Klaudia Walter, Josine L. Min, Ioanna Tachmazidou, Giovanni Malerba,So-Youn Shin, Lu Chen, Marta Futema, Lorraine Southam, Valentina Iotchkova,Massimiliano Cocca, Jie Huang, Yasin Memari, Shane McCarthy, Petr Danecek, Dawn Muddyman, Massimo Mangino, Cristina Menni, John R. B. Perry, Susan M. Ring et al.

The analysis of rich catalogues of genetic variation from population-based sequencing provides an opportunity to screen for functional effects. Here we report a rare variant in ​APOC3 (rs138326449-A, minor allele frequency ~0.25% (UK)) associated with plasma triglyceride (TG) levels (−1.43 s.d. (s.e.=0.27 per minor allele (P-value=8.0 × 10−8)) discovered in 3,202 individuals with low read-depth, whole-genome sequence. We replicate this in 12,831 participants from five additional samples of Northern and Southern European origin (−1.0 s.d. (s.e.=0.173), P-value=7.32 × 10−9). This is consistent with an effect between 0.5 and 1.5 mmol l−1 dependent on population. We show that a single predicted splice donor variant is responsible for association signals and is independent of known common variants. Analyses suggest an independent relationship between rs138326449 and high-density lipoprotein (HDL) levels. This represents one of the first examples of a rare, large effect variant identified from whole-genome sequencing at a population scale.

来源: Nature中文 浏览次数:92

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