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, MAlan, 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, LK, Mihailov, E, Miller, MB, Minica, CC, Nolte, IM, Mook-Kanamori, DO, van der Most, PJ, Oldmeadow, CJ, Qian, Y, Raitakari, OT, Rawal, R, Realo, A, Rueedi, R, Schmidt, B, Smith, AVernon, Stergiakouli, E, Tanaka, T, Taylor, KD, 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, AJ, 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, AAE, 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, A. Thurik, R, Timpson, NJ, Tiemeier, H, Uitterlinden, AG, Vollenweider, P, Wagner, GG, Weir, DR, Yang, J, Conley, DC, Hofman, A, Johannesson, M, Laibson, DI, Medland, SE, Meyer, MN, Pickrell, JK, Esko, T, Krueger, RF, Beauchamp, JP, Koellinger, PD, Benjamin, DJ, Bartels, M, Cesarini, D
Corporate AuthorsLifeLines Cohort Study
JournalNat Genet
Volume48
Issue6
Pagination624-33
Date Published2016 06
ISSN Number1546-1718
KeywordsAnxiety Disorders, Bayes Theorem, depression, Genome-Wide Association Study, Humans, Neuroticism, Phenotype, Polymorphism, Single Nucleotide
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
User Guide Notes

http://www.ncbi.nlm.nih.gov/pubmed/27089181?dopt=Abstract

Alternate JournalNat. Genet.
Citation Key8618
PubMed ID27089181
PubMed Central IDPMC4884152
Grant ListR01 DA036216 / DA / NIDA NIH HHS / United States
G1001799 / / Medical Research Council / United Kingdom
RF1 AG015819 / AG / NIA NIH HHS / United States
U01 AG009740 / AG / NIA NIH HHS / United States
MC_UU_12013/3 / / Medical Research Council / United Kingdom
MC_QA137853 / / Medical Research Council / United Kingdom
R01 AG017917 / AG / NIA NIH HHS / United States
MR/J012165/1 / / Medical Research Council / United Kingdom
R03 AG051960 / AG / NIA NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
MR/K026992/1 / / Medical Research Council / United Kingdom
MR/N01104X/1 / / Medical Research Council / United Kingdom
P30 DK063491 / DK / NIDDK NIH HHS / United States
P2C HD047879 / HD / NICHD NIH HHS / United States
MC_PC_15018 / / Medical Research Council / United Kingdom
P30 AG010161 / AG / NIA NIH HHS / United States
MC_UU_12013/1 / / Medical Research Council / United Kingdom
MC_PC_U127561128 / / Medical Research Council / United Kingdom
P01 AG005842 / AG / NIA NIH HHS / United States
R37 DA005147 / DA / NIDA NIH HHS / United States
P30 AG012810 / AG / NIA NIH HHS / United States
R01 AG042568 / AG / NIA NIH HHS / United States
T32 AG000186 / AG / NIA NIH HHS / United States
647648 / / European Research Council / International