Neuroscience Research Australia, Sydney, NSW, Australia.
School of Psychology, University of New South Wales, Sydney, NSW, Australia.
Transl Psychiatry. 2022 Mar 19;12(1):113. doi: 10.1038/s41398-022-01874-5.
Wellbeing is an important aspect of mental health that is moderately heritable. Specific wellbeing-related variants have been identified via GWAS meta-analysis of individual questionnaire items. However, a multi-item within-subject index score has potential to capture greater heritability, enabling improved delineation of genetic and phenotypic relationships across traits and exposures that are not possible on aggregate-data. This research employed data from the UK Biobank resource, and a wellbeing index score was derived from indices of happiness and satisfaction with family/friendship/finances/health, using principal component analysis. GWAS was performed in Caucasian participants (N = 129,237) using the derived wellbeing index, followed by polygenic profiling (independent sample; N = 23,703). The wellbeing index, its subcomponents, and negative indicators of mental health were compared via phenotypic and genetic correlations, and relationships with psychiatric disorders examined. Lastly, the impact of childhood maltreatment on wellbeing was investigated. Five independent genome-wide significant loci for wellbeing were identified. The wellbeing index had SNP-heritability of ~8.6%, and stronger phenotypic and genetic correlations with its subcomponents (0.55-0.77) than mental health phenotypes (-0.21 to -0.39). The wellbeing score was lower in participants reporting various psychiatric disorders compared to the total sample. Childhood maltreatment exposure was also associated with reduced wellbeing, and a moderate genetic correlation (r = ~-0.56) suggests an overlap in heritability of maltreatment with wellbeing. Thus, wellbeing is negatively associated with both psychiatric disorders and childhood maltreatment. Although notable limitations, biases and assumptions are discussed, this within-cohort study aids the delineation of relationships between a quantitative wellbeing index and indices of mental health and early maltreatment.
幸福感是心理健康的一个重要方面，具有适度的遗传性。通过对个体问卷项目的 GWAS 荟萃分析，已经确定了特定的与幸福感相关的变异。然而，多项目的个体内指数得分有可能捕捉到更大的遗传性，从而能够更好地描述遗传和表型关系，包括在综合数据中无法实现的跨特征和暴露的关系。这项研究利用了英国生物库资源的数据，并使用主成分分析从幸福感和对家庭/友谊/财务/健康的满意度指数中得出幸福感指数得分。在高加索参与者（N=129237）中进行了 GWAS，使用派生的幸福感指数，随后进行了多基因分析（独立样本；N=23703）。通过表型和遗传相关性比较了幸福感指数及其子成分和心理健康的负向指标，并研究了与精神障碍的关系。最后，研究了儿童期虐待对幸福感的影响。确定了幸福感的五个独立全基因组显著位点。幸福感指数的 SNP 遗传率约为 8.6%，与幸福感的子成分（0.55-0.77）比心理健康表型（0.21-0.39）具有更强的表型和遗传相关性。与总样本相比，报告各种精神障碍的参与者的幸福感指数较低。童年期虐待的暴露也与幸福感降低有关，中等的遗传相关性（r=~-0.56）表明虐待与幸福感的遗传重叠。因此，幸福感与精神障碍和儿童期虐待均呈负相关。尽管存在显著的局限性、偏见和假设，但这项队列内研究有助于阐明定量幸福感指数与心理健康和早期虐待指数之间的关系。
