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

TitleGenetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses.
Publication TypeJournal Article
Year of Publication2016
AuthorsOkbay, A, Baselmans, BML, De Neve, J-E, Turley, P, Nivard, MG, Fontana, MA, S Meddens, FW, Linnér, RKarlsson, Rietveld, CA, Derringer, J, Gratten, J, Lee, JJ, Liu, JZ, de Vlaming, R, Ahluwalia, TS, Buchwald, J, Cavadino, A, Frazier-Wood, AC, Furlotte, NA, Garfield, V, Geisel, MHenrike, Gonzalez, JR, Haitjema, S, Karlsson, R, van der Laan, SW, Ladwig, K-H, Lahti, J, van der Lee, SJ, Lind, PA, Liu, T, Matteson, L, Mihailov, E, Miller, MB, Minica, CC, Nolte, IM, Mook-Kanamori, DO, van der Most, PJ, Oldmeadow, C, Qian, Y, Raitakari, OT, Rawal, R, Realo, A, Rueedi, R, Schmidt, B, Smith, AVernon, Stergiakouli, E, Tanaka, T, Taylor, K, Wedenoja, J, Wellmann, J, Westra, H-J, Willems, SM, Zhao, W, Amin, N, Bakshi, A, Boyle, PA, Cherney, S, Cox, SR, Davies, G, Davis, OSP, Ding, J, Direk, N, Eibich, P, Emeny, RT, Fatemifar, G, Faul, JD, Ferrucci, L, Forstner, A, Gieger, C, Gupta, R, Harris, TB, Harris, JM, Holliday, EG, Hottenga, J-J, De Jager, PL, Kaakinen, MA, Kajantie, E, Karhunen, V, Kolcic, I, Kumari, M, Launer, LJ, Franke, LL, Li-Gao, R, Koini, M, Loukola, A, Marques-Vidal, P, Montgomery, GW, Mosing, MA, Paternoster, L, Pattie, A, Petrovic, KE, Pulkki-Raback, L, Quaye, L, Räikkönen, K, Rudan, I, Scott, RJ, Smith, JA, Sutin, AR, Trzaskowski, M, Vinkhuyzen, AE, Yu, L, Zabaneh, D, Attia, JR, Bennett, DA, Berger, K, Bertram, L, Boomsma, DI, Snieder, H, Chang, S-C, Cucca, F, Deary, IJ, van Duijn, CM, Eriksson, JG, Bültmann, U, de Geus, EJC, Groenen, PJF, Gudnason, V, Hansen, T, Hartman, CA, Haworth, CMA, Hayward, C, Heath, AC, Hinds, DA, Hyppönen, E, Iacono, WG, Järvelin, M-R, Jöckel, K-H, Kaprio, J, Kardia, SLR, Keltikangas-Järvinen, L, Kraft, P, Kubzansky, LD, Lehtimäki, T, Magnusson, PKE, Martin, NG, McGue, M, Metspalu, A, Mills, MC, de Mutsert, R, Oldehinkel, AJ, Pasterkamp, G, Pedersen, NL, Plomin, R, Polasek, O, Power, C, Rich, SS, Rosendaal, FR, den Ruijter, HM, Schlessinger, D, Schmidt, H, Svento, R, Schmidt, R, Alizadeh, BZ, Sørensen, TIA, Spector, TD, Steptoe, A, Terracciano, A, Thurik, AR, Timpson, NJ, Tiemeier, H, Uitterlinden, AG, Vollenweider, P, Wagner, GG, Weir, DR, Yang, J, Dalton C. Conley, Hofman, A, Johannesson, M, Laibson, DI, Medland, SE, Meyer, MN, Pickrell, JK, Esko, T, Krueger, RF, Jonathan P. Beauchamp, Koellinger, P, Benjamin, DJ, Bartels, M, Cesarini, D
Corporate AuthorsLifeLines Cohort Study
JournalNature Genetics
Volume48
Issue6
Pagination624-33
Date Published2016 Jun
ISSN Number1546-1718
KeywordsCHARGE, Depressive symptoms, Genetics, Mental Illness, Meta-analyses, Older Adults
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.

DOI10.1038/ng.3552
Alternate JournalNat. Genet.
Citation Key8618
PubMed ID27089181
PubMed Central IDPMC4884152
Grant ListP01 AG005842 / AG / NIA NIH HHS / United States
P30 AG012810 / AG / NIA NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
R01 AG042568 / AG / NIA NIH HHS / United States
T32 AG000186 / AG / NIA NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States