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

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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 Lees, Jimmy Z Liu, Ronald De Vlaming, Tarunveer S Ahluwalia, Jadwiga Buchwald, Alana Cavadino, Alexis C Frazier-wood, Nicholas A Furlotte, Victoria Garfield & 160 others Marie 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, Juergen Wellmann, Harm-jan Westra, Sara M Willems, Wei Zhao, Najaf Amin, Andrew Bakshi, Patricia A Boyle, Samantha Cherney, Simon R Cox, Gail Davies, Oliver S P Davis, Jun Ding, Nese Direk, Peter Eibich, Rebecca T Emeny, Ghazaleh Fatemifar, Jessica D Faul, Luigi Ferrucci, Andreas Forstner, Christian Gieger, Richa Gupta, Tamara B Harris, Juliette M Harris, Elizabeth G Holliday, Jouke-jan Hottenga, Philip L De Jager, Marika A Kaakinen, Eero Kajantie, Ville Karhunen, Ivana Kolcic, Meena Kumari, Lenore J Launer, Lude Franke, Ruifang Li-gao, Marisa Koini, Anu Loukola, Pedro Marques-vidal, Grant W Montgomery, Miriam A Mosing, Lavinia Paternoster, Alison Pattie, Katja E Petrovic, Laura Pulkki-råback, Lydia Quaye, Katri Räikkönen, Igor Rudan, Rodney J Scott, Jennifer A Smith, Angelina R Sutin, Maciej Trzaskowski, Anna E Vinkhuyzen, Lei Yu, Delilah Zabaneh, John R Attia, David A Bennett, Klaus Berger, Lars Bertram, Dorret I Boomsma, Harold Snieder, Shun-chiao Chang, Francesco Cucca, Ian J Deary, Cornelia M Van Duijn, Johan G Eriksson, Ute Bültmann, Eco J C De Geus, Patrick J F Groenen, Vilmundur Gudnason, Torben Hansen, Catharine A Hartman, Claire M A Haworth, Caroline Hayward, Andrew C Heath, David A Hinds, Elina Hyppönen, William G Iacono, Marjo-riitta Järvelin, Karl-heinz Jöckel, Jaakko Kaprio, Sharon L R Kardia, Liisa Keltikangas-järvinen, Peter Kraft, Laura D Kubzansky, Terho Lehtimäki, Patrik K E Magnusson, Nicholas G Martin, Matt Mcgue, Andres Metspalu, Melinda Mills, Renée De Mutsert, Albertine J Oldehinkel, Gerard Pasterkamp, Nancy L Pedersen, Robert Plomin, Ozren Polasek, Christine Power, Stephen S Rich, Frits R Rosendaal, Hester M Den Ruijter, David Schlessinger, Helena Schmidt, Rauli Svento, Reinhold Schmidt, Behrooz Z Alizadeh, Thorkild I A Sørensen, Tim D Spector, Andrew Steptoe, Antonio Terracciano, A Roy Thurik, Nicholas J Timpson, Henning Tiemeier, André G Uitterlinden, Peter Vollenweider, Gert G Wagner, David R Weir, Jian Yang, Dalton C Conley, George Davey Smith, Albert Hofman, Magnus Johannesson, David I Laibson, Sarah E Medland, Michelle N Meyer, Joseph K Pickrell, Tõnu Esko, Robert F Krueger, Jonathan P Beauchamp, Philipp D Koellinger, Daniel J Benjamin, Meike Bartels, David Cesarini

Original languageEnglish
JournalNature Genetics
Early online date18 Apr 2016
DOIs
Publication statusE-pub ahead of print - 18 Apr 2016

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Abstract

ery 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 (|ρˆ| ≈ 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.

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