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Nature Research, Nature Genetics, 6(48), p. 624-633, 2016

DOI: 10.1038/ng.3552

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Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

Journal article published in 2016 by Cornelia M. van Duijn, Hester M. den Ruijter, Sander W. van der Laan, Sven J. van der Lee ORCID, Peter J. van der Most ORCID, P. L. de Jager, Eco J. C. de Geus ORCID, Renée de Mutsert, J.-E. de Neve, Ronald de Vlaming, Sara M. Willems, der Laan Sw Van, der Lee Sj Van, Aysu Okbay, Jan-Emmanuel De Neve and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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.