Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses.
Okbay A., Baselmans BML., De Neve J-E., Turley P., Nivard MG., Fontana MA., Meddens SFW., Linnér RK., 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 MH., 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 D., van der Most PJ., Oldmeadow C., Qian Y., Raitakari O., Rawal R., Realo A., Rueedi R., Schmidt B., Smith AV., Stergiakouli E., Tanaka T., Taylor K., Thorleifsson G., Wedenoja J., Wellmann J., Westra H-J., Willems SM., Zhao W., LifeLines Cohort Study None., Amin N., Bakshi A., Bergmann S., Bjornsdottir G., 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 L., Li-Gao R., Liewald DC., Koini M., Loukola A., Marques-Vidal P., Montgomery GW., Mosing MA., Paternoster L., Pattie A., Petrovic KE., Pulkki-Råback 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 M., 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., Starr JM., Stefansson K., Steptoe A., Terracciano A., Thorsteinsdottir U., Thurik AR., Timpson NJ., Tiemeier H., Uitterlinden AG., Vollenweider P., Wagner GG., Weir DR., Yang J., Conley DC., Smith GD., 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.
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.