利用条件错误发现率方法识别欧洲人群抑郁症与大脑海马体新的遗传位点

Identification of novel genetic loci associated with major depressive disorder and the hippocampus in a European population using the condFDR method

目的利用全基因组关联研究识别更多与抑郁症和海马体相关的遗传变异位点。方法本研究数据来自精神疾病遗传学联盟和英国生物银行(UK Biobank)数据库,全基因组关联研究(GWAS)数据涉及170756例抑郁症和329443例对照,左右侧海马体积GWAS数据涉及33224名参与者。利用条件错误发现率(condFDR)识别抑郁症和左右侧海马体积新的遗传位点,联合错误发现率(conjFDR)评估抑郁症和左右侧海马体积之间的多效性位点的富集程度。结果在condFDR<0.01的水平上,识别了7个新位点和抑郁症相关,13个新位点和左海马体积相关,12个新位点和右海马体积相关。在conjFDR<0.01的水平上,确定了一个与抑郁症和右侧海马体积相关的遗传位点rs1267073。结论全基因组关联研究识别海马体和抑郁症风险的遗传机制为未来的抑郁症治疗试验提供依据。

Objective To identify additional loci associated with depression and the hippocampus(HIP)through genome-wide association study.Methods The depression-related genome-wide association study(GWAS)meta summary data was downloaded from the official website of the Psychiatric Genomics Consortium,which had involved 170756 cases and 329443 controls.The left and right hippocampal volume GWAS data sets were downloaded from the UK Biobank,which involved 33224 participants.The conditional false discovery rate(condFDR)was used to identify novel genetic loci for depression and left and right hippocampal volumes,and a conjunctional false discovery rate(conjFDR)was used to evaluate the enrichment of pleiotropic loci between depression and left and right hippocampal volumes.Results Respectively,7,13,and 12 new loci have been associated with depression,left hippocampal volume and right hippocampal volume,with a significant threshold of condFDR<0.01.A site of rs1267073 locus was found to be shared by the depression and right hippocampal volume with a threshold of conjFDR<0.01.Conclusion Above findings have provided more insights into the genetic mechanisms underlying the volume of hippocampus and the risk for depression.The results may also provide evidence for future clinical trials for treating depression.