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The cis and trans effects of the risk variants of coronary artery disease in the Chr9p21 region

机译：Chr9p21区冠状动脉疾病风险变异的顺式和反式作用

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Background Recent genome-wide association studies (GWAS) have shown that single nucleotide polymorphisms (SNPs) in the Chr9p21 region are associated with coronary artery disease (CAD). Most of the SNPs identified in this region are non-coding SNPs, suggesting that they may influence gene expression by cis or trans mechanisms to affect disease susceptibility. Since all cells from an individual have the same DNA sequence variations, levels of gene expression in immortalized cell lines can reflect the functional effects of DNA sequence variations that influence or regulate gene expression. The objective of this study is to evaluate the functional consequences of the risk variants in the Chr9p21 region on gene expression. Methods We examined the association between the variants in the Chr9p21 region and the transcript-level mRNA expression of the adjacent genes ( cis ) as well as all other genes across the whole genome ( trans ) from transformed beta-lymphocytes in 801 non-Hispanic white participants from The Genetic Epidemiology Network of Arteriopathy (GENOA) study. Results We found that the CAD risk variants in the Chr9p21 region were significantly associated with the mRNA expression of the ANRIL transcript ENST00000428597 (p?=?8.58e-06) . Importantly, a few distant transcripts were also found to be associated with the variants in this region, including the well-known CAD risk gene ABCA1 (p?=?1.01e-05). Gene enrichment testing suggests that retinol metabolism, N-Glycan biosynthesis, and TGF signaling pathways may be involved. Conclusion These results suggest that the effect of risk variants in the Chr9p21 region on susceptibility to CAD is likely to be mediated through both cis and trans mechanisms.
机译：背景技术最近的全基因组关联研究（GWAS）显示，Chr9p21区的单核苷酸多态性（SNP）与冠状动脉疾病（CAD）相关。在该区域中鉴定出的大多数SNP是非编码SNP，这表明它们可能通过顺式或反式机制影响疾病易感性而影响基因表达。由于来自个体的所有细胞都具有相同的DNA序列变异，因此永生化细胞系中基因表达的水平可以反映影响或调节基因表达的DNA序列变异的功能效应。这项研究的目的是评估Chr9p21区域中的风险变异对基因表达的功能后果。方法我们研究了801个非西班牙裔白人中Chr9p21区域中的变异与邻近基因（顺式）以及整个基因组（反式）中所有其他基因的转录水平mRNA表达之间的关联遗传疾病的流行病学网络（GENOA）研究的参与者。结果我们发现Chr9p21区域中的CAD风险变体与ANRIL转录物ENST00000428597的mRNA表达显着相关（p≥8.58e-06）。重要的是，还发现一些远距离的转录本与该区域的变体有关，包括众所周知的CAD危险基因ABCA1（p≥1.01e-05）。基因富集测试表明，可能涉及视黄醇代谢，N-聚糖的生物合成和TGF信号通路。结论这些结果表明，Chr9p21区风险变异对CAD敏感性的影响可能是通过顺式和反式机制介导的。

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