Association analyses based on false discovery rate implicate new loci for coronary artery disease
Association analyses based on false discovery rate implicate new loci for coronary artery disease
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DOI：
10.1038/ng.3913
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发表时间：
2017-09-01
期刊：
影响因子：
30.8
通讯作者：
Deloukas, Panos
中科院分区：
文献类型：
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作者：
Nelson, Christopher P.;Goel, Anuj;Deloukas, Panos
冠状动脉疾病（CAD）的全基因组关联研究（GWAS）在本分析时已确定了66个具有“全基因组显著性”（P < 5 x 10（-8））的基因座，但更多的推定基因座的错误发现率（FDR）为5%（参考文献10）。第1-4段）。在这里，我们利用英国生物银行（UKBB）数据的临时发布来评估FDR方法的有效性。我们测试了包括心绞痛的CAD表型（SOFT; n（病例）= 10，801）以及不包括心绞痛的更严格定义（HARD; n（病例）= 6，482），并选择具有前一表型的病例，使用两个最新的CAD GWAS进行荟萃分析（2，3）。该方法鉴定了13个具有全基因组显著性的新基因座，其中12个在我们之前的满足5%FDR阈值的基因座列表中（2），从而为FDR鉴定的其余基因座代表真正的信号提供了强有力的支持。在这项研究中，与5%FDR相关的304个独立变异解释了21.2%的CAD遗传性，并确定了243个涉及血管形态发生以及脂质代谢、一氧化氮信号传导和炎症途径的基因座。
Genome-wide association studies (GWAS) in coronary artery disease (CAD) had identified 66 loci at 'genome-wide significance' (P < 5 x 10(-8)) at the time of this analysis, but a much larger number of putative loci at a false discovery rate (FDR) of 5% (refs. 1-4). Here we leverage an interim release of UK Biobank (UKBB) data to evaluate the validity of the FDR approach. We tested a CAD phenotype inclusive of angina (SOFT; n(cases) = 10,801) as well as a stricter definition without angina (HARD; n(cases) = 6,482) and selected cases with the former phenotype to conduct a meta-analysis using the two most recent CAD GWAS(2,3). This approach identified 13 new loci at genome-wide significance, 12 of which were on our previous list of loci meeting the 5% FDR threshold(2), thus providing strong support that the remaining loci identified by FDR represent genuine signals. The 304 independent variants associated at 5% FDR in this study explain 21.2% of CAD heritability and identify 243 loci that implicate pathways in blood vessel morphogenesis as well as lipid metabolism, nitric oxide signaling and inflammation.