Abstract
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(g) = ~-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.