Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.
Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Nat Neurosci. 2019 Mar;22(3):343-352. doi: 10.1038/s41593-018-0326-7. Epub 2019 Feb 4.
Major depression is a debilitating psychiatric illness that is typically associated with low mood and anhedonia. Depression has a heritable component that has remained difficult to elucidate with current sample sizes due to the polygenic nature of the disorder. To maximize sample size, we meta-analyzed data on 807,553 individuals (246,363 cases and 561,190 controls) from the three largest genome-wide association studies of depression. We identified 102 independent variants, 269 genes, and 15 genesets associated with depression, including both genes and gene pathways associated with synaptic structure and neurotransmission. An enrichment analysis provided further evidence of the importance of prefrontal brain regions. In an independent replication sample of 1,306,354 individuals (414,055 cases and 892,299 controls), 87 of the 102 associated variants were significant after multiple testing correction. These findings advance our understanding of the complex genetic architecture of depression and provide several future avenues for understanding etiology and developing new treatment approaches.
重度抑郁症是一种使人虚弱的精神疾病，通常与情绪低落和快感缺失有关。抑郁症具有遗传性，由于这种疾病的多基因性质，目前的样本量很难阐明。为了最大限度地增加样本量，我们对来自三大抑郁症全基因组关联研究的 807553 个人（246363 例病例和 561190 例对照）的数据进行了荟萃分析。我们确定了 102 个独立的变异、269 个基因和 15 个与抑郁症相关的基因集，包括与突触结构和神经递质传递相关的基因和基因途径。富集分析进一步提供了证据，证明了前额叶脑区的重要性。在独立的 1306354 人复制样本（414055 例病例和 892299 例对照）中，在多重检验校正后，102 个相关变异中有 87 个具有统计学意义。这些发现增进了我们对抑郁症复杂遗传结构的理解，并为理解病因和开发新的治疗方法提供了几个未来的途径。
