Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions
Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions
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DOI：
10.1038/s41593-018-0326-7
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发表时间：
2019-03-01
影响因子：
25
通讯作者：
McIntosh, Andrew M.
中科院分区：
文献类型：
--
作者：
Howard, David M.;Adams, Mark J.;McIntosh, Andrew M.
重度抑郁症是一种使人衰弱的精神疾病，通常与情绪低落和快感缺乏有关。抑郁症具有遗传性，由于该疾病的多基因性质，目前的样本量仍然难以阐明。为了最大化样本量，我们对来自三项最大的抑郁症全基因组关联研究的 807,553 名个体（246,363 例病例和 561,190 名对照）的数据进行了荟萃分析。我们鉴定了与抑郁症相关的 102 个独立变异、269 个基因和 15 个基因组，包括与突触结构和神经传递相关的基因和基因通路。富集分析进一步证明了前额叶大脑区域的重要性。在 1,306,354 个人（414,055 例病例和 892,299 对照）的独立复制样本中，102 个相关变异中有 87 个在多重测试校正后显着。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一些未来的途径。
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 neuro-transmission. 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.