Distinguishing happiness and meaning in life from depressive symptoms: A GWAS‐by‐subtraction study in the UK Biobank

Abstract

Hedonic (happiness) and eudaimonic (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 overlap and differences between well‐being and depressive symptoms, using results of Genome‐Wide Association studies (GWAS) in UK Biobank. Subtracting 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 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 0.78 to 0.65. Pure happiness and pure meaning became genetically unrelated to traits strongly associated with depressive symptoms, including loneliness, and psychiatric disorders. For other traits, including ADHD, educational attainment, and smoking, the genetic correlations of well‐being versus pure well‐being changed substantially. GWAS‐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. Our results can be used as a starting point to test causal relationships with other variables, and design future well‐being interventions.

The stability and change of wellbeing across the lifespan: a longitudinal twin-sibling study

“…However, in contrast, only genetic innovation in adolescence was found for wellbeing, whereas for anxiety and depression during both childhood and adolescence there was significant genetic innovation. Furthermore, recently, we showed unique genetic aspects of wellbeing, independently from depressive symptoms in our recent GWAS-by-subtraction study (de Vries et al, 2024). The slightly different longitudinal results on wellbeing and depressive symptoms indicate as well that the patterns of genetic and unique environmental factors throughout life are not completely mirror images for wellbeing and depressive symptoms.…”

Assessment of the Genetic Characteristics of a Generation Born during a Long-Term Socioeconomic Crisis

“…There is a substantial genetic overlap between well-being and depressive symptoms. In a recent article on UK Biobank data, subtracting the "depressive symptoms" GWAS from the "happiness and meaning of life" GWASs revealed that ADHD and risk taking have a direct genetic correlation with well-being [84]. Perhaps such a subtractive approach in the future will enable researchers to separate the adaptive and maladaptive genetic components of increased anxiety.…”