Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism

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Koellinger PD, Benjamin DJ, Bartels M, Cesarini D. Genetic variants associated

with subjective well-being, depressive symptoms, and neuroticism identified

through genome-wide analyses. Nat Genet. 2016 Jun;48(6):624-33.

Abstract

Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.

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From the article

Subjective well-being—as measured by survey questions on life satisfaction, positive affect, or happiness—is a major topic of research in psychology, economics, and epidemiology. Twin studies have found that subjective well-being is genetically correlated with depression (characterized by negative affect, anxiety, low energy, bodily aches and pains, pessimism, and other symptoms) and neuroticism (a personality trait characterized by easily experiencing negative emotions such as anxiety and fear). Depression and neuroticism have received much more attention than subjective well-being in genetic association studies, but the discovery of genetic variants associated with either of them has proven elusive.

Here we report a series of separate and joint analyses of subjective well-being, depressive symptoms, and neuroticism, which identify 16 genome-wide significant associations across the three phenotypes. In our two joint analyses, we exploit the high genetic correlation between subjective well-being, depressive symptoms, and neuroticism (i) to evaluate the credibility of the associations from our initial genome-wide association study (GWAS) and (ii) to identify new associations (beyond those identified by the GWAS)...

We found significant enrichment of central nervous system for all three phenotypes and, perhaps more surprisingly, enrichment of adrenal/pancreas for subjective well-being and depressive symptoms. The cause of the adrenal/pancreas enrichment is unclear, but we note that the adrenal glands produce several hormones, including cortisol, epinephrine, and norepinephrine, known to have important roles in the bodily regulation of mood and stress. It has been robustly found that blood serum levels of cortisol in patients afflicted by depression are elevated relative to those in controls.