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全基因组关联研究鉴定出阿拉伯人群中高甘油三酯的新型隐性遗传变异。

Genome-wide association study identifies novel recessive genetic variants for high TGs in an Arab population.

机构信息

Dasman Diabetes Institute, Dasman 15462, Kuwait.

Faculty of Medicine, Univerisity of Helsinki, Helsinki, Finland.

出版信息

J Lipid Res. 2018 Oct;59(10):1951-1966. doi: 10.1194/jlr.P080218. Epub 2018 Aug 14.

Abstract

Abnormal blood lipid levels are influenced by genetic and lifestyle/dietary factors. Although many genetic variants associated with blood lipid traits have been identified in Europeans, similar data in Middle Eastern populations are limited. We performed a genome-wide association study with Arab individuals (discovery cohort: 1,353; replication cohort: 1,176) from Kuwait to identify possible associations of genetic variants with high lipid levels. We used Illumina HumanOmniExpress BeadChip and candidate SNP genotyping in the discovery and replication phases, respectively. For association tests, we used genetic models that were based on additive and recessive modes of inheritance. High triglycerides (TGs) were recessively associated with six risk variants (rs1002487/, rs11805972/) rs7761746/, rs39745/-, rs2934952/, and rs9626773/-) at genome-wide significance (  6.12E-09), and another six variants (rs10873925/, rs4663379/, rs10033119/, rs17709449/-, rs11654954/, and rs9972882/) were associated at borderline significance (  5.0E-08). High TG was also additively associated with rs11654954. All of the 12 identified markers are novel and are harbored in runs of homozygosity. Literature evidence supports the involvement of these gene loci in lipid-related processes. This study in an Arab population augments international efforts to identify genetic regulation of lipid traits.

摘要

血脂水平异常受遗传和生活方式/饮食因素的影响。虽然在欧洲人群中已经确定了许多与血脂特征相关的遗传变异,但在中东人群中类似的数据有限。我们对来自科威特的阿拉伯个体(发现队列:1353;复制队列:1176)进行了全基因组关联研究,以确定遗传变异与高血脂水平的可能关联。我们分别在发现和复制阶段使用了 Illumina HumanOmniExpress BeadChip 和候选 SNP 基因分型。对于关联测试,我们使用了基于加性和隐性遗传模式的遗传模型。高甘油三酯(TGs)与六个风险变异(rs1002487/,rs11805972/,rs7761746/,rs39745/-,rs2934952/,和 rs9626773/-) 呈隐性相关,达到全基因组显著性水平(  6.12E-09),另外六个变异(rs10873925/,rs4663379/,rs10033119/,rs17709449/,rs11654954/,和 rs9972882/) 呈边缘显著性相关(  5.0E-08)。高 TG 还与 rs11654954 呈加性相关。所有 12 个鉴定的标记均为新发现,且位于纯合子连续区。文献证据支持这些基因座参与脂质相关过程。本研究在阿拉伯人群中的开展,增加了国际上对脂质特征遗传调控的研究力度。

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