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

Aysu Okbay, Bart M L Baselmans, Jan-Emmanuel De Neve, Patrick Turley, Michel G Nivard, Mark Alan Fontana, S Fleur W Meddens, Richard Karlsson Linnér, Cornelius A Rietveld, Jaime Derringer, Jacob Gratten, James J Lee, Jimmy Z Liu, Ronald de Vlaming, Tarunveer S Ahluwalia, Jadwiga Buchwald, Alana Cavadino, Alexis C Frazier-Wood, Nicholas A Furlotte, Victoria GarfieldMarie Henrike Geisel, Juan R Gonzalez, Saskia Haitjema, Robert Karlsson, Sander W van der Laan, Karl-Heinz Ladwig, Jari Lahti, Sven J van der Lee, Penelope A Lind, Tian Liu, Lindsay Matteson, Evelin Mihailov, Michael B Miller, Camelia C Minica, Ilja M Nolte, Dennis Mook-Kanamori, Peter J van der Most, Christopher Oldmeadow, Yong Qian, Olli Raitakari, Rajesh Rawal, Anu Realo, Rico Rueedi, Börge Schmidt, Albert V Smith, Evie Stergiakouli, Toshiko Tanaka, Kent Taylor, Juho Wedenoja, Thorkild I A Sørensen, LifeLines Cohort Study

636 Citations (Scopus)

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.

Original languageEnglish
JournalNature Genetics
Volume48
Issue number6
Pages (from-to)624-33
Number of pages10
ISSN1061-4036
DOIs
Publication statusPublished - Jun 2016

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