de Vries, L. P. | Search bioRxiv

bioRxiv2022

Distinguishing Happiness and Meaning in Life from Depressive Symptoms: a GWAS-by-subtraction study in the UK Biobank

BackgroundHedonic (e.g., happiness) and eudaimonic (e.g., meaning in life) well-being are negatively related to depressive symptoms. Genetic variants play a role in this association, reflected in substantial genetic correlations. We investigated the (genetic) overlap and differences between well-being and depressive symptoms. MethodsWe used results of Genome-Wide Association studies (GWAS) and applied GWAS-by-subtraction in the UK Biobank sample. Analyses were pre-registered. ResultsSubtracting GWAS summary statistics of depressive symptoms from those of happiness and meaning in life, we obtained GWASs of respectively pure happiness (neffective= 216,497) and pure meaning" (neffective=102,300). For both, we identified one genome-wide significant SNP (rs1078141 and rs79520962, respectively). After the subtraction, SNP heritability reduced from 6.3% to 3.3% for pure happiness and from 6.2% to 4.2% for pure meaning. The genetic correlation between the well-being measures reduced from .78 to .65, indicating that only a part of the genetic overlap between happiness and meaning in life is due to overlap with depressive symptoms. Pure happiness and pure meaning became genetically unrelated to traits strongly associated with depressive symptoms, including tiredness, loneliness, and psychiatric disorders. For several other traits, including ADHD, income, educational attainment, smoking, and drinking alcohol, the genetic correlations of well-being versus pure well-being changed substantially. ConclusionsGWAS-by-subtraction allowed us to investigate the genetic variance of well-being unrelated to depressive symptoms. Genetic correlations with different traits led to new insights about this unique part of well-being. The findings can have implications for interventions to increase well-being and/or decrease depressive symptoms.

genetics↗

bioRxiv2020

Genetic evidence for bidirectional causal effects between resilience and well-being.

Resilience and well-being are strongly related. People with higher levels of well-being are more resilient after stressful life events or trauma and vice versa. Less is known about the underlying sources of overlap and causality between the constructs. In a sample of 11.304 twins and 2.572 siblings from the Netherlands Twin Register, we investigated the overlap and possible direction of causation between resilience (i.e. the absence of psychiatric symptoms despite negative life events) and well-being (i.e. satisfaction with life) using polygenic score (PGS) prediction, twin-sibling modelling, and the Mendelian Randomization Direction of Causality (MR-DoC) model. Longitudinal twin-sibling models showed significant phenotypic correlations between resilience and well-being (.41/.51 at time 1 and 2). Well-being PGS were predictive for both well-being and resilience, indicating that genetic factors influencing well-being also predict resilience. Twin-sibling modeling confirmed this genetic correlation (.71) and showed a strong environmental correlation (.93). In line with causality, both genetic (51%) and environmental (49%) factors contributed significantly to the covariance between resilience and well-being. Furthermore, the results of within-subject and MZ twin differences analyses were in line with bidirectional causality. Additionally, we used the MR-DoC model combining both molecular and twin data to test causality, while correcting for pleiotropy. We confirmed the causal effect from well-being to resilience, with the direct effect of well-being explaining 11% (T1) and 20% (T2) of the variance in resilience. Data limitations prevented us to test the directional effect from resilience to well-being with the MR-DoC model. To conclude, we showed a strong relation between well-being and resilience. A first attempt to quantify the direction of this relationship points towards a bidirectional causal effect. If replicated, the potential mutual effects can have implications for interventions to lower psychopathology vulnerability, as resilience and well-being are both negatively related to psychopathology.

genetics↗