Translational Neurogenomics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia.
Nat Hum Behav. 2021 Oct;5(10):1432-1442. doi: 10.1038/s41562-021-01094-9. Epub 2021 Apr 15.
Depression and anxiety are highly prevalent and comorbid psychiatric traits that cause considerable burden worldwide. Here we use factor analysis and genomic structural equation modelling to investigate the genetic factor structure underlying 28 items assessing depression, anxiety and neuroticism, a closely related personality trait. Symptoms of depression and anxiety loaded on two distinct, although highly genetically correlated factors, and neuroticism items were partitioned between them. We used this factor structure to conduct genome-wide association analyses on latent factors of depressive symptoms (89 independent variants, 61 genomic loci) and anxiety symptoms (102 variants, 73 loci) in the UK Biobank. Of these associated variants, 72% and 78%, respectively, replicated in an independent cohort of approximately 1.9 million individuals with self-reported diagnosis of depression and anxiety. We use these results to characterize shared and trait-specific genetic associations. Our findings provide insight into the genetic architecture of depression and anxiety and comorbidity between them.
抑郁和焦虑是高度普遍且共患的精神疾病特征，在全球范围内造成了相当大的负担。在这里，我们使用因子分析和基因组结构方程模型来研究评估抑郁、焦虑和神经质（一种密切相关的人格特征）的 28 个项目的遗传因素结构。抑郁和焦虑的症状加载在两个不同的、尽管高度遗传相关的因素上，而神经质的项目则在它们之间进行划分。我们使用这种因子结构，在英国生物库中对抑郁症状的潜在因子（89 个独立变体，61 个基因组位点）和焦虑症状（102 个变体，73 个位点）进行全基因组关联分析。在大约 190 万自我报告患有抑郁和焦虑症的独立队列中，分别有 72%和 78%的这些相关变体得到了复制。我们使用这些结果来描述共同和特质特异性的遗传关联。我们的研究结果为抑郁和焦虑及其共病的遗传结构提供了深入的了解。
