Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore; and Khoo Teck Puat - National University Children's Medical Institute, National University Health System, Singapore, Singapore.
Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.
Sci Rep. 2017 Dec 20;7(1):17921. doi: 10.1038/s41598-017-18214-z.
Recent genome-wide association studies (GWAS) have identified multiple loci associated with coronary artery disease (CAD) among predominantly Europeans. However, their relevance to multi-ethnic populations from Southeast Asia is largely unknown. We performed a meta-analysis of four GWAS comprising three Chinese studies and one Malay study (Total N = 2,169 CAD cases and 7,376 controls). Top hits (P < 5 × 10) were further evaluated in 291 CAD cases and 1,848 controls of Asian Indians. Using all datasets, we validated recently identified loci associated with CAD. The involvement of known canonical pathways in CAD was tested by Ingenuity Pathway Analysis. We identified a missense SNP (rs2075291, G > T, G185C) in APOA5 for CAD that reached robust genome-wide significance (Meta P = 7.09 × 10, OR = 1.636). Conditional probability analysis indicated that the association at rs2075291 was independent of previously reported index SNP rs964184 in APOA5. We further replicated 10 loci previously identified among predominantly Europeans (P: 1.33 × 10-0.047). Seven pathways (P: 1.10 × 10-0.019) were identified. We identified a missense SNP, rs2075291, in APOA5 associated with CAD at a genome-wide significance level and provided new insights into pathways contributing to the susceptibility to CAD in the multi-ethnic populations from Southeast Asia.
最近的全基因组关联研究（GWAS）已经确定了多个与冠状动脉疾病（CAD）相关的基因座，这些基因座主要存在于欧洲人群中。然而，它们与东南亚多民族人群的相关性在很大程度上尚不清楚。我们对四项 GWAS 进行了荟萃分析，其中包括三项中国研究和一项马来研究（总病例数为 2169 例，对照组为 7376 例）。对 291 例亚洲印第安人 CAD 病例和 1848 例对照进行了最高命中（P < 5×10）的进一步评估。使用所有数据集，我们验证了最近与 CAD 相关的已确定基因座。通过 Ingenuity Pathway Analysis 测试了 CAD 中已知经典途径的参与情况。我们在 APOA5 中发现了一个与 CAD 相关的错义 SNP（rs2075291，G > T，G185C），该 SNP 在全基因组范围内达到了显著水平（Meta P = 7.09×10，OR = 1.636）。条件概率分析表明，rs2075291 的相关性独立于先前报道的 APOA5 中的索引 SNP rs964184。我们进一步复制了在主要为欧洲人群中发现的 10 个基因座（P：1.33×10-0.047）。确定了 7 条途径（P：1.10×10-0.019）。我们在 APOA5 中发现了一个错义 SNP，rs2075291，与 CAD 相关，达到了全基因组显著水平，并为东南亚多民族人群对 CAD 易感性的途径提供了新的见解。
