Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity
Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity
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DOI：
10.1038/s41467-018-08008-w
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发表时间：
2019-01-22
影响因子：
16.6
通讯作者：
Loos, Ruth J. F.
中科院分区：
文献类型：
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作者：
Kilpelainen, Tuomas O.;Bentley, Amy R.;Loos, Ruth J. F.
许多遗传位点影响循环脂质水平，但尚不清楚生活方式因素，如体育活动，是否会改变这些遗传效应。为了确定与体力活动相互作用的脂质位点，我们对来自欧洲、非洲、亚洲、西班牙和巴西血统的多达120，979名个体的循环HDL胆固醇、LDL胆固醇和甘油三酯水平进行了全基因组分析，并对另外131，012名个体进行了暗示性关联的随访。我们发现CLASP 1、LHX 1、SNTA 1和CNTNAP 2中/附近的四个基因座通过与体力活动的相互作用与循环脂质水平相关;更高水平的体力活动增强CLASP 1、LHX 1和SNTA 1基因座的HDL胆固醇增加效应，并减弱CNTNAP 2基因座的LDL胆固醇增加效应。CLASP 1、LHX 1和SNTA 1区域含有与肌肉功能和脂质代谢相关的基因。我们的研究结果阐明了身体活动的相互作用在遗传对血脂水平的贡献中的作用。
Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol- increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.