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

Aysu Okbay, BML Baselmans, JE De Neve, P Turley, MG Nivard, MA Fontana, SFW Meddens, RK Linner, CA Rietveld, J Derringer, J Gratten, JJ Lee, JZ Liu, R de Vlaming, TS Ahluwalia, J Buchwald, A Cavadino, AC Frazier-Wood, NA Furlotte, V GarfieldMH Geisel, JR Gonzalez, S Haitjema, R Karlsson, Sander Laan, KH Ladwig, J Lahti, Sven van der Lee, PA Lind, T Liu, L Matteson, E Mihailov, MB Miller, CC Minica, IM (Ilja) Nolte, D Mook-Kanamori, PJ van der Most, C Oldmeadow, Y Qian, O Raitakari, R Rawal, A Realo, R Rueedi, B Schmidt, AV Smith, E Stergiakouli, T Tanaka, K Taylor, J Wedenoja, J Wellmann, HJ Westra, SM Willems, W Zhao, Najaf Amin, A Bakshi, PA Boyle, S Cherney, SR Cox, G Davies, OSP Davis, J Ding, Nese Direk, P Eibich, RT Emeny, G Fatemifar, JD Faul, L Ferrucci, A Forstner, C Gieger, R Gupta, TB Harris, JM Harris, EG Holliday, JJ (Jouke Jan) Hottenga, PL De Jager, MA Kaakinen, E Kajantie, V Karhunen, I Kolcic, M Kumari, LJ (Lenore) Launer, L Franke, R Li-Gao, M Koini, A Loukola, P Marques-Vidal, GW Montgomery, MA Mosing, L Paternoster, A Pattie, KE Petrovic, L Pulkki-Raback, L Quaye, K Raikkonen, I Rudan, RJ Scott, JA Smith, AR Sutin, M Trzaskowski, AE Vinkhuyzen, L Yu, D Zabaneh, JR Attia, DA Bennett, K Berger, L Bertram, DI Boomsma, H Snieder, SC Chang, F Cucca, IJ Deary, Cornelia Duijn, JG Eriksson, U Bultmann, EJC de Geus, PJF Groenen, V Gudnason, T Hansen, CA Hartman, CMA Haworth, C Hayward, AC Heath, DA Hinds, E Hypponen, WG Iacono, MR Jarvelin, KH Jockel, J Kaprio, SLR Kardia, L Keltikangas-Jarvinen, P Kraft, LD Kubzansky, T Lehtimaki, PKE Magnusson, NG Martin, M McGue, A Metspalu, M Mills, R de Mutsert, AJ (A.) Oldehinkel, G Pasterkamp, NL Pedersen, R Plomin, O Polasek, C Power, SS Rich, FR Rosendaal, HM den Ruijter, D Schlessinger, Heléna Schmidt, R Svento, R Schmidt, BZ Alizadeh, TIA Sorensen, TD Spector, A Steptoe, A Terracciano, AR Thurik, NJ Timpson, Henning Tiemeier, André Uitterlinden, P Vollenweider, GG Wagner, DR Weir, Jiaqi Yang, DC Conley, GD Smith, Bert Hofman, M Johannesson, DI Laibson, SE Medland, MN Meyer, JK Pickrell, T Esko, RF Krueger, JP Beauchamp, PD Koellinger, DJ Benjamin, MC Bartels, D Cesarini

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519 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 (vertical bar(p) over cap vertical bar approximate to 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
Pages (from-to)624-633
Number of pages10
JournalNature Genetics
Volume48
Issue number6
DOIs
Publication statusPublished - 2016

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