Hyde Craig L, Nagle Michael W, Tian Chao, Chen Xing, Paciga Sara A, Wendland Jens R, Tung Joyce Y, Hinds David A, Perlis Roy H, Winslow Ashley R
Statistics, Pfizer Global Research and Development, Pfizer, Inc., Cambridge, Massachusetts, USA.
Human Genetics and Computational Biomedicine, Pfizer Global Research and Development, Pfizer, Inc., Cambridge, Massachusetts, USA.
Nat Genet. 2016 Sep;48(9):1031-6. doi: 10.1038/ng.3623. Epub 2016 Aug 1.
Despite strong evidence supporting the heritability of major depressive disorder (MDD), previous genome-wide studies were unable to identify risk loci among individuals of European descent. We used self-report data from 75,607 individuals reporting clinical diagnosis of depression and 231,747 individuals reporting no history of depression through 23andMe and carried out meta-analysis of these results with published MDD genome-wide association study results. We identified five independent variants from four regions associated with self-report of clinical diagnosis or treatment for depression. Loci with a P value <1.0 × 10(-5) in the meta-analysis were further analyzed in a replication data set (45,773 cases and 106,354 controls) from 23andMe. A total of 17 independent SNPs from 15 regions reached genome-wide significance after joint analysis over all three data sets. Some of these loci were also implicated in genome-wide association studies of related psychiatric traits. These studies provide evidence for large-scale consumer genomic data as a powerful and efficient complement to data collected from traditional means of ascertainment for neuropsychiatric disease genomics.
尽管有强有力的证据支持重度抑郁症(MDD)的遗传性,但先前的全基因组研究未能在欧洲血统个体中确定风险基因座。我们使用了来自75607名报告有抑郁症临床诊断的个体以及231747名通过23andMe报告无抑郁症病史的个体的自我报告数据,并将这些结果与已发表的MDD全基因组关联研究结果进行了荟萃分析。我们从与抑郁症临床诊断或治疗的自我报告相关的四个区域中确定了五个独立变异。在荟萃分析中P值<1.0×10⁻⁵的基因座在来自23andMe的一个复制数据集(45773例病例和106354例对照)中进一步分析。在对所有三个数据集进行联合分析后,来自15个区域的总共17个独立单核苷酸多态性(SNP)达到全基因组显著性。其中一些基因座也与相关精神疾病性状的全基因组关联研究有关。这些研究为大规模消费者基因组数据作为从传统确定方法收集的数据在神经精神疾病基因组学方面的强大而有效的补充提供了证据。