利用条件错误发现率方法识别欧洲人群炎症性肠病相关位点

Improved detection of loci associated with inflammatory bowel disease in European populations using the cFDR method

目的:利用更高效的数据分析方法识别更多与炎症性肠病相关的遗传变异位点。方法:炎症性肠病的全基因组关联研究(GWAS)汇总数据来源于国际炎症性肠病遗传学联合会官网,其中,溃疡性结肠炎(UC)相关的GWAS meta汇总数据涉及20 464个对照和6 968个病例;克罗恩病(CD)相关的GWAS meta汇总数据涉及14 927个对照和5 956个病例。首先利用条件Q-Q图和条件真实发现率(TDR)图评估疾病之间多效性富集程度;再计算SNPs的条件错误发现率(c FDR)和联合的条件错误发现率(cc FDR),以0.01为显著性阈值筛选与疾病相关的遗传位点。结果:一共识别了43个新位点和UC相关;86个新位点和CD相关;22个新位点与UC和CD都相关。结论:新识别的这些遗传位点为研究UC和CD的遗传和致病机制提供了新的线索。

Aim： To identify more loci associated with inflammatory bowel disease（ IBD） by using the cost-effective analytical methods. Methods： The IBD related genome wide association study（ GWAS） meta summary data sets were downloaded from the official website of the International Inflammatory Bowel Disease Genetics Consortium. The ulcerative colitis（ UC） related GWAS meta summary data including 20 464 controls and 6 968 cases,and the crohn＇ s disease（ CD）related GWAS meta summary data involving 14 927 controls and 5 956 cases were collected. Firstly,we used the conditional quantile-quantile（ Q-Q） plots and the conditional true discovery rate（ TDR） plots to assess the degree of the pleiotropic enrichment between these two diseases. Then we calculated the conditional false discovery rate（ c FDR） and conjunction c FDR（ cc FDR） for each SNP,if the c FDR or cc FDR of a SNP was smaller than the significant threshold（0. 01）,the SNP was associated with the disease. Results： A total of 43 novel loci for UC and 86 novel loci for CD were identified with a significant threshold of c FDR 0. 01. And 22 novel loci were identified for both UC and CD. Conclusion： These novel loci provide us novel insights into the etiology of UC and CD.