Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Nat Commun. 2020 May 8;11(1):2301. doi: 10.1038/s41467-020-16022-0.
Depression is a leading cause of worldwide disability but there remains considerable uncertainty regarding its neural and behavioural associations. Here, using non-overlapping Psychiatric Genomics Consortium (PGC) datasets as a reference, we estimate polygenic risk scores for depression (depression-PRS) in a discovery (N = 10,674) and replication (N = 11,214) imaging sample from UK Biobank. We report 77 traits that are significantly associated with depression-PRS, in both discovery and replication analyses. Mendelian Randomisation analysis supports a potential causal effect of liability to depression on brain white matter microstructure (β: 0.125 to 0.868, p < 0.043). Several behavioural traits are also associated with depression-PRS (β: 0.014 to 0.180, p: 0.049 to 1.28 × 10) and we find a significant and positive interaction between depression-PRS and adverse environmental exposures on mental health outcomes. This study reveals replicable associations between depression-PRS and white matter microstructure. Our results indicate that white matter microstructure differences may be a causal consequence of liability to depression.
抑郁症是全球致残的主要原因，但人们对其与神经和行为的关联仍存在很大的不确定性。在这里，我们使用相互独立的精神疾病基因组学联盟（PGC）数据集作为参考，在来自英国生物库的一个发现（N=10674）和复制（N=11214）影像样本中，对抑郁症的多基因风险评分（depression-PRS）进行了估计。我们报告了在发现和复制分析中与 depression-PRS 显著相关的 77 个特征。孟德尔随机化分析支持抑郁症易感性对大脑白质微观结构的潜在因果影响（β：0.125 至 0.868，p<0.043）。一些行为特征也与 depression-PRS 相关（β：0.014 至 0.180，p：0.049 至 1.28×10），我们发现 depression-PRS 与不良环境暴露对心理健康结果之间存在显著的正相互作用。本研究揭示了 depression-PRS 与白质微观结构之间可重复的关联。我们的结果表明，白质微观结构的差异可能是抑郁症易感性的一个因果后果。
