NORMENT, KG Jebsen Centre for Neurodevelopmental Disorders, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Bjørknes College, Oslo, Norway.
Transl Psychiatry. 2021 Apr 1;11(1):202. doi: 10.1038/s41398-021-01313-x.
Genome-wide association studies (GWAS) and family-based studies have revealed partly overlapping genetic architectures between various psychiatric disorders. Given clinical overlap between disorders, our knowledge of the genetic architectures underlying specific symptom profiles and risk factors is limited. Here, we aimed to derive distinct profiles relevant to mental health in healthy individuals and to study how these genetically relate to each other and to common psychiatric disorders. Using independent component analysis, we decomposed self-report mental health questionnaires from 136,678 healthy individuals of the UK Biobank, excluding data from individuals with a diagnosed neurological or psychiatric disorder, into 13 distinct profiles relevant to mental health, capturing different symptoms as well as social and risk factors underlying reduced mental health. Utilizing genotypes from 117,611 of those individuals with White British ancestry, we performed GWAS for each mental health profile and assessed genetic correlations between these profiles, and between the profiles and common psychiatric disorders and cognitive traits. We found that mental health profiles were genetically correlated with a wide range of psychiatric disorders and cognitive traits, with strongest effects typically observed between a given mental health profile and a disorder for which the profile is common (e.g. depression symptoms and major depressive disorder, or psychosis and schizophrenia). Strikingly, although the profiles were phenotypically uncorrelated, many of them were genetically correlated with each other. This study provides evidence that statistically independent mental health profiles partly share genetic underpinnings and show genetic overlap with psychiatric disorders, suggesting that shared genetics across psychiatric disorders cannot be exclusively attributed to the known overlapping symptomatology between the disorders.
全基因组关联研究（GWAS）和基于家庭的研究揭示了各种精神障碍之间部分重叠的遗传结构。鉴于障碍之间存在临床重叠，我们对特定症状特征和风险因素背后遗传结构的了解是有限的。在这里，我们旨在从健康个体中得出与心理健康相关的不同特征，并研究这些特征如何相互遗传以及与常见精神障碍相关。使用独立成分分析，我们从英国生物库的 136678 名健康个体的自我报告心理健康问卷中分解出 13 个与心理健康相关的不同特征，这些特征捕捉到了不同的症状以及导致心理健康下降的社会和风险因素。利用来自具有白种英国人种的 117611 名个体的基因型，我们对每个心理健康特征进行了 GWAS，并评估了这些特征之间以及这些特征与常见精神障碍和认知特征之间的遗传相关性。我们发现，心理健康特征与广泛的精神障碍和认知特征具有遗传相关性，通常在给定的心理健康特征与该特征常见的障碍之间观察到最强的效应（例如抑郁症状和重度抑郁症，或精神病和精神分裂症）。引人注目的是，尽管这些特征在表型上不相关，但其中许多在遗传上相互相关。这项研究提供了证据表明，统计学上独立的心理健康特征部分共享遗传基础，并与精神障碍存在遗传重叠，这表明精神障碍之间的共享遗传学不能仅仅归因于这些障碍之间已知的重叠症状。
