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

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 J. Lee; Jimmy Z. Liu; Ronald De Vlaming; Tarunveer SAhluwalia; Jadwiga Buchwald; Alana Cavadino; Alexis C. Frazier-Wood; Nicholas A. Furlotte; Victoria Garfield; Marie Henrike Geisel; Juan R. Gonzalez; Saskia Haitjema; Robert Karlsson; Sander Wvan 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 CMinica; Ilja MNolte; 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 MWillems; Wei Zhao; Life Lines Cohort Study; 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-R'back; Lydia Quaye; Katri R'ikkönen; Igor Rudan; Rodney J. Scott; Jennifer A. Smith; Angelina R. Sutin; Maciej Trzaskowski; Anna E. Vinkhuyze; 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 Cde 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 J'rvelin; Karl Heinz Jöckel; Jaakko Kaprio; Sharon L R Kardia; Liisa Keltikangas-J'rvinen; Peter Kraft; Laura D. Kubzansky; Terho Lehtim'ki; 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 DSpector; 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; T'nu Esko; Robert F. Krueger; Jonathan P. Beauchamp; Philipp D. Koellinger; Daniel J. Benjamin; Meike Bartels; David Cesarini

doi:10.1038/ng.3552

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

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 J. Lee, Jimmy Z. Liu, Ronald De Vlaming, Tarunveer SAhluwalia, Jadwiga Buchwald, Alana Cavadino, Alexis C. Frazier-Wood, Nicholas A. Furlotte, Victoria GarfieldMarie Henrike Geisel, Juan R. Gonzalez, Saskia Haitjema, Robert Karlsson, Sander Wvan 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 CMinica, Ilja MNolte, 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 MWillems, Wei Zhao, Life Lines Cohort Study, 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-R'back, Lydia Quaye, Katri R'ikkönen, Igor Rudan, Rodney J. Scott, Jennifer A. Smith, Angelina R. Sutin, Maciej Trzaskowski, Anna E. Vinkhuyze, 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 Cde 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 J'rvelin, Karl Heinz Jöckel, Jaakko Kaprio, Sharon L R Kardia, Liisa Keltikangas-J'rvinen, Peter Kraft, Laura D. Kubzansky, Terho Lehtim'ki, 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 DSpector, 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, T'nu Esko, Robert F. Krueger, Jonathan P. Beauchamp, Philipp D. Koellinger, Daniel J. Benjamin, Meike Bartels, David Cesarini

Psychology (Twin Cities)

Research output: Contribution to journal › Article › peer-review

595 Scopus citations

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 (P = 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 language	English (US)
Pages (from-to)	624-633
Number of pages	10
Journal	Nature Genetics
Volume	48
Issue number	6
DOIs	https://doi.org/10.1038/ng.3552
State	Published - Jun 1 2016

Bibliographical note

Funding Information:
We are grateful to P.M. Visscher for advice, support, and feedback. We thank S. Cunningham and N. Galla for research assistance. This research was carried out under the auspices of the Social Science Genetic Association Consortium (SSGAC). The SSGAC seeks to facilitate studies that investigate the influence of genes on human behavior, well-being, and social-scientific outcomes using large GWAS meta-analyses. The SSGAC also provides opportunities for replication and promotes the collection of accurately measured, harmonized phenotypes across cohorts. The SSGAC operates as a working group within the CHARGE Consortium. This research has also been conducted using the UK Biobank Resource. The study was supported by funding from the US National Science Foundation (EAGER: 'Workshop for the Formation of a Social Science Genetic Association Consortium'), a supplementary grant from the National Institute of Health Office of Behavioral and Social Science Research, the Ragnar Söderberg Foundation (E9/11), the Swedish Research Council (421-2013-1061), the Jan Wallander and Tom Hedelius Foundation, an ERC Consolidator Grant (647648 EdGe), the Pershing Square Fund of the Foundations of Human Behavior, and the NIA/NIH through grants P01-AG005842, P01-AG005842-20S2, P30-AG012810, and T32-AG000186-23 to NBER and R01-AG042568-02 to the University of Southern California. A full list of acknowledgments is provided

Publisher Copyright:
© 2016 Nature America, Inc.

Publisher link

10.1038/ng.3552

http://europepmc.org/articles/pmc4884152

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Okbay, A., Baselmans, B. M. L., De Neve, J. E., Turley, P., Nivard, M. G., Fontana, M. A., Meddens, S. F. W., Linnér, R. K., Rietveld, C. A., Derringer, J., Gratten, J., Lee, J. J., Liu, J. Z., De Vlaming, R., SAhluwalia, T., Buchwald, J., Cavadino, A., Frazier-Wood, A. C., Furlotte, N. A., ... Cesarini, D. (2016). Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. Nature Genetics, 48(6), 624-633. https://doi.org/10.1038/ng.3552

Okbay, A, Baselmans, BML, De Neve, JE, Turley, P, Nivard, MG, Fontana, MA, Meddens, SFW, Linnér, RK, Rietveld, CA, Derringer, J, Gratten, J, Lee, JJ, Liu, JZ, De Vlaming, R, SAhluwalia, T, Buchwald, J, Cavadino, A, Frazier-Wood, AC, Furlotte, NA, Garfield, V, Geisel, MH, Gonzalez, JR, Haitjema, S, Karlsson, R, Der Laan, SW, Ladwig, KH, Lahti, J, Van Der Lee, SJ, Lind, PA, Liu, T, Matteson, L, Mihailov, E, Miller, MB, CMinica, C, MNolte, I, 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, Wedenoja, J, Wellmann, J, Westra, HJ, MWillems, S, Zhao, W, Study, LLC, 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, JJ, De Jager, PL, Kaakinen, MA, Kajantie, E, Karhunen, V, Kolcic, I, Kumari, M, Launer, LJ, Franke, L, Li-Gao, R, Koini, M, Loukola, A, Marques-Vidal, P, Montgomery, GW, Mosing, MA, Paternoster, L, Pattie, A, Petrovic, KE, Pulkki-R'back, L, Quaye, L, R'ikkönen, K, Rudan, I, Scott, RJ, Smith, JA, Sutin, AR, Trzaskowski, M, Vinkhuyze, AE, Yu, L, Zabaneh, D, Attia, JR, Bennett, DA, Berger, K, Bertram, L, Boomsma, DI, Snieder, H, Chang, SC, Cucca, F, Deary, IJ, Van Duijn, CM, Eriksson, JG, Bültmann, U, Geus, EJC, Groenen, PJF, Gudnason, V, Hansen, T, Hartman, CA, Haworth, CMA, Hayward, C, Heath, AC, Hinds, DA, Hyppönen, E, Iacono, WG, J'rvelin, MR, Jöckel, KH, Kaprio, J, Kardia, SLR, Keltikangas-J'rvinen, L, Kraft, P, Kubzansky, LD, Lehtim'ki, 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, DSpector, T, Steptoe, A, Terracciano, A, 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 2016, 'Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses', Nature Genetics, vol. 48, no. 6, pp. 624-633. https://doi.org/10.1038/ng.3552

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

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 (P = 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.",

author = "Aysu Okbay and Baselmans, {Bart M L} and {De Neve}, {Jan Emmanuel} and Patrick Turley and Nivard, {Michel G.} and Fontana, {Mark Alan} and Meddens, {S. Fleur W} and Linn{\'e}r, {Richard Karlsson} and Rietveld, {Cornelius A.} and Jaime Derringer and Jacob Gratten and Lee, {James J.} and Liu, {Jimmy Z.} and {De Vlaming}, Ronald and Tarunveer SAhluwalia and Jadwiga Buchwald and Alana Cavadino and Frazier-Wood, {Alexis C.} and Furlotte, {Nicholas A.} and Victoria Garfield and Geisel, {Marie Henrike} and Gonzalez, {Juan R.} and Saskia Haitjema and Robert Karlsson and {Der Laan}, {Sander Wvan} and Ladwig, {Karl Heinz} and Jari Lahti and {Van Der Lee}, {Sven J.} and Lind, {Penelope A.} and Tian Liu and Lindsay Matteson and Evelin Mihailov and Miller, {Michael B.} and Camelia CMinica and Ilja MNolte and Dennis Mook-Kanamori and {Van Der Most}, {Peter J.} and Christopher Oldmeadow and Yong Qian and Olli Raitakari and Rajesh Rawal and Anu Realo and Rico Rueedi and B{\"o}rge Schmidt and Smith, {Albert V.} and Evie Stergiakouli and Toshiko Tanaka and Kent Taylor and Juho Wedenoja and Juergen Wellmann and Westra, {Harm Jan} and Sara MWillems and Wei Zhao and Study, {Life Lines Cohort} and Najaf Amin and Andrew Bakshi and Boyle, {Patricia A.} and Samantha Cherney and Cox, {Simon R.} and Gail Davies and Davis, {Oliver S P} and Jun Ding and Nese Direk and Peter Eibich and Emeny, {Rebecca T.} and Ghazaleh Fatemifar and Faul, {Jessica D.} and Luigi Ferrucci and Andreas Forstner and Christian Gieger and Richa Gupta and Harris, {Tamara B.} and Harris, {Juliette M.} and Holliday, {Elizabeth G.} and Hottenga, {Jouke Jan} and {De Jager}, {Philip L.} and Kaakinen, {Marika A.} and Eero Kajantie and Ville Karhunen and Ivana Kolcic and Meena Kumari and Launer, {Lenore J.} and Lude Franke and Ruifang Li-Gao and Marisa Koini and Anu Loukola and Pedro Marques-Vidal and Montgomery, {Grant W.} and Mosing, {Miriam A.} and Lavinia Paternoster and Alison Pattie and Petrovic, {Katja E.} and Laura Pulkki-R'back and Lydia Quaye and Katri R'ikk{\"o}nen and Igor Rudan and Scott, {Rodney J.} and Smith, {Jennifer A.} and Sutin, {Angelina R.} and Maciej Trzaskowski and Vinkhuyze, {Anna E.} and Lei Yu and Delilah Zabaneh and Attia, {John R.} and Bennett, {David A.} and Klaus Berger and Lars Bertram and Boomsma, {Dorret I.} and Harold Snieder and Chang, {Shun Chiao} and Francesco Cucca and Deary, {Ian J.} and {Van Duijn}, {Cornelia M.} and Eriksson, {Johan G.} and Ute B{\"u}ltmann and Geus, {Eco J Cde} and Groenen, {Patrick J F} and Vilmundur Gudnason and Torben Hansen and Hartman, {Catharine A.} and Haworth, {Claire M A} and Caroline Hayward and Heath, {Andrew C.} and Hinds, {David A.} and Elina Hypp{\"o}nen and Iacono, {William G.} and J'rvelin, {Marjo Riitta} and J{\"o}ckel, {Karl Heinz} and Jaakko Kaprio and Kardia, {Sharon L R} and Liisa Keltikangas-J'rvinen and Peter Kraft and Kubzansky, {Laura D.} and Terho Lehtim'ki and Magnusson, {Patrik K E} and Martin, {Nicholas G.} and Matt McGue and Andres Metspalu and Melinda Mills and {De Mutsert}, Ren{\'e}e and Oldehinkel, {Albertine J.} and Gerard Pasterkamp and Pedersen, {Nancy L.} and Robert Plomin and Ozren Polasek and Christine Power and Rich, {Stephen S.} and Rosendaal, {Frits R.} and {Den Ruijter}, {Hester M.} and David Schlessinger and Helena Schmidt and Rauli Svento and Reinhold Schmidt and Alizadeh, {Behrooz Z.} and S{\O}rensen, {Thorkild I A} and Tim DSpector and Andrew Steptoe and Antonio Terracciano and Thurik, {A. Roy} and Timpson, {Nicholas J.} and Henning Tiemeier and Uitterlinden, {Andr{\'e} G.} and Peter Vollenweider and Wagner, {Gert G.} and Weir, {David R.} and Jian Yang and Conley, {Dalton C.} and Smith, {George Davey} and Albert Hofman and Magnus Johannesson and Laibson, {David I.} and Medland, {Sarah E.} and Meyer, {Michelle N.} and Pickrell, {Joseph K.} and T'nu Esko and Krueger, {Robert F.} and Beauchamp, {Jonathan P.} and Koellinger, {Philipp D.} and Benjamin, {Daniel J.} and Meike Bartels and David Cesarini",

note = "Funding Information: We are grateful to P.M. Visscher for advice, support, and feedback. We thank S. Cunningham and N. Galla for research assistance. This research was carried out under the auspices of the Social Science Genetic Association Consortium (SSGAC). The SSGAC seeks to facilitate studies that investigate the influence of genes on human behavior, well-being, and social-scientific outcomes using large GWAS meta-analyses. The SSGAC also provides opportunities for replication and promotes the collection of accurately measured, harmonized phenotypes across cohorts. The SSGAC operates as a working group within the CHARGE Consortium. This research has also been conducted using the UK Biobank Resource. The study was supported by funding from the US National Science Foundation (EAGER: 'Workshop for the Formation of a Social Science Genetic Association Consortium'), a supplementary grant from the National Institute of Health Office of Behavioral and Social Science Research, the Ragnar S{\"o}derberg Foundation (E9/11), the Swedish Research Council (421-2013-1061), the Jan Wallander and Tom Hedelius Foundation, an ERC Consolidator Grant (647648 EdGe), the Pershing Square Fund of the Foundations of Human Behavior, and the NIA/NIH through grants P01-AG005842, P01-AG005842-20S2, P30-AG012810, and T32-AG000186-23 to NBER and R01-AG042568-02 to the University of Southern California. A full list of acknowledgments is provided Publisher Copyright: {\textcopyright} 2016 Nature America, Inc.",

year = "2016",

month = jun,

day = "1",

doi = "10.1038/ng.3552",

language = "English (US)",

volume = "48",

pages = "624--633",

journal = "Nature Genetics",

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publisher = "Nature Publishing Group",

number = "6",

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TY - JOUR

T1 - Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

AU - Okbay, Aysu

AU - Baselmans, Bart M L

AU - De Neve, Jan Emmanuel

AU - Turley, Patrick

AU - Nivard, Michel G.

AU - Fontana, Mark Alan

AU - Meddens, S. Fleur W

AU - Linnér, Richard Karlsson

AU - Rietveld, Cornelius A.

AU - Derringer, Jaime

AU - Gratten, Jacob

AU - Lee, James J.

AU - Liu, Jimmy Z.

AU - De Vlaming, Ronald

AU - SAhluwalia, Tarunveer

AU - Buchwald, Jadwiga

AU - Cavadino, Alana

AU - Frazier-Wood, Alexis C.

AU - Furlotte, Nicholas A.

AU - Garfield, Victoria

AU - Geisel, Marie Henrike

AU - Gonzalez, Juan R.

AU - Haitjema, Saskia

AU - Karlsson, Robert

AU - Der Laan, Sander Wvan

AU - Ladwig, Karl Heinz

AU - Lahti, Jari

AU - Van Der Lee, Sven J.

AU - Lind, Penelope A.

AU - Liu, Tian

AU - Matteson, Lindsay

AU - Mihailov, Evelin

AU - Miller, Michael B.

AU - CMinica, Camelia

AU - MNolte, Ilja

AU - Mook-Kanamori, Dennis

AU - Van Der Most, Peter J.

AU - Oldmeadow, Christopher

AU - Qian, Yong

AU - Raitakari, Olli

AU - Rawal, Rajesh

AU - Realo, Anu

AU - Rueedi, Rico

AU - Schmidt, Börge

AU - Smith, Albert V.

AU - Stergiakouli, Evie

AU - Tanaka, Toshiko

AU - Taylor, Kent

AU - Wedenoja, Juho

AU - Wellmann, Juergen

AU - Westra, Harm Jan

AU - MWillems, Sara

AU - Zhao, Wei

AU - Study, Life Lines Cohort

AU - Amin, Najaf

AU - Bakshi, Andrew

AU - Boyle, Patricia A.

AU - Cherney, Samantha

AU - Cox, Simon R.

AU - Davies, Gail

AU - Davis, Oliver S P

AU - Ding, Jun

AU - Direk, Nese

AU - Eibich, Peter

AU - Emeny, Rebecca T.

AU - Fatemifar, Ghazaleh

AU - Faul, Jessica D.

AU - Ferrucci, Luigi

AU - Forstner, Andreas

AU - Gieger, Christian

AU - Gupta, Richa

AU - Harris, Tamara B.

AU - Harris, Juliette M.

AU - Holliday, Elizabeth G.

AU - Hottenga, Jouke Jan

AU - De Jager, Philip L.

AU - Kaakinen, Marika A.

AU - Kajantie, Eero

AU - Karhunen, Ville

AU - Kolcic, Ivana

AU - Kumari, Meena

AU - Launer, Lenore J.

AU - Franke, Lude

AU - Li-Gao, Ruifang

AU - Koini, Marisa

AU - Loukola, Anu

AU - Marques-Vidal, Pedro

AU - Montgomery, Grant W.

AU - Mosing, Miriam A.

AU - Paternoster, Lavinia

AU - Pattie, Alison

AU - Petrovic, Katja E.

AU - Pulkki-R'back, Laura

AU - Quaye, Lydia

AU - R'ikkönen, Katri

AU - Rudan, Igor

AU - Scott, Rodney J.

AU - Smith, Jennifer A.

AU - Sutin, Angelina R.

AU - Trzaskowski, Maciej

AU - Vinkhuyze, Anna E.

AU - Yu, Lei

AU - Zabaneh, Delilah

AU - Attia, John R.

AU - Bennett, David A.

AU - Berger, Klaus

AU - Bertram, Lars

AU - Boomsma, Dorret I.

AU - Snieder, Harold

AU - Chang, Shun Chiao

AU - Cucca, Francesco

AU - Deary, Ian J.

AU - Van Duijn, Cornelia M.

AU - Eriksson, Johan G.

AU - Bültmann, Ute

AU - Geus, Eco J Cde

AU - Groenen, Patrick J F

AU - Gudnason, Vilmundur

AU - Hansen, Torben

AU - Hartman, Catharine A.

AU - Haworth, Claire M A

AU - Hayward, Caroline

AU - Heath, Andrew C.

AU - Hinds, David A.

AU - Hyppönen, Elina

AU - Iacono, William G.

AU - J'rvelin, Marjo Riitta

AU - Jöckel, Karl Heinz

AU - Kaprio, Jaakko

AU - Kardia, Sharon L R

AU - Keltikangas-J'rvinen, Liisa

AU - Kraft, Peter

AU - Kubzansky, Laura D.

AU - Lehtim'ki, Terho

AU - Magnusson, Patrik K E

AU - Martin, Nicholas G.

AU - McGue, Matt

AU - Metspalu, Andres

AU - Mills, Melinda

AU - De Mutsert, Renée

AU - Oldehinkel, Albertine J.

AU - Pasterkamp, Gerard

AU - Pedersen, Nancy L.

AU - Plomin, Robert

AU - Polasek, Ozren

AU - Power, Christine

AU - Rich, Stephen S.

AU - Rosendaal, Frits R.

AU - Den Ruijter, Hester M.

AU - Schlessinger, David

AU - Schmidt, Helena

AU - Svento, Rauli

AU - Schmidt, Reinhold

AU - Alizadeh, Behrooz Z.

AU - SØrensen, Thorkild I A

AU - DSpector, Tim

AU - Steptoe, Andrew

AU - Terracciano, Antonio

AU - Thurik, A. Roy

AU - Timpson, Nicholas J.

AU - Tiemeier, Henning

AU - Uitterlinden, André G.

AU - Vollenweider, Peter

AU - Wagner, Gert G.

AU - Weir, David R.

AU - Yang, Jian

AU - Conley, Dalton C.

AU - Smith, George Davey

AU - Hofman, Albert

AU - Johannesson, Magnus

AU - Laibson, David I.

AU - Medland, Sarah E.

AU - Meyer, Michelle N.

AU - Pickrell, Joseph K.

AU - Esko, T'nu

AU - Krueger, Robert F.

AU - Beauchamp, Jonathan P.

AU - Koellinger, Philipp D.

AU - Benjamin, Daniel J.

AU - Bartels, Meike

AU - Cesarini, David

N1 - Funding Information: We are grateful to P.M. Visscher for advice, support, and feedback. We thank S. Cunningham and N. Galla for research assistance. This research was carried out under the auspices of the Social Science Genetic Association Consortium (SSGAC). The SSGAC seeks to facilitate studies that investigate the influence of genes on human behavior, well-being, and social-scientific outcomes using large GWAS meta-analyses. The SSGAC also provides opportunities for replication and promotes the collection of accurately measured, harmonized phenotypes across cohorts. The SSGAC operates as a working group within the CHARGE Consortium. This research has also been conducted using the UK Biobank Resource. The study was supported by funding from the US National Science Foundation (EAGER: 'Workshop for the Formation of a Social Science Genetic Association Consortium'), a supplementary grant from the National Institute of Health Office of Behavioral and Social Science Research, the Ragnar Söderberg Foundation (E9/11), the Swedish Research Council (421-2013-1061), the Jan Wallander and Tom Hedelius Foundation, an ERC Consolidator Grant (647648 EdGe), the Pershing Square Fund of the Foundations of Human Behavior, and the NIA/NIH through grants P01-AG005842, P01-AG005842-20S2, P30-AG012810, and T32-AG000186-23 to NBER and R01-AG042568-02 to the University of Southern California. A full list of acknowledgments is provided Publisher Copyright: © 2016 Nature America, Inc.

PY - 2016/6/1

Y1 - 2016/6/1

N2 - 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 (P = 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.

AB - 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 (P = 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.

UR - http://www.scopus.com/inward/record.url?scp=84964388798&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84964388798&partnerID=8YFLogxK

U2 - 10.1038/ng.3552

DO - 10.1038/ng.3552

M3 - Article

C2 - 27089181

AN - SCOPUS:84964388798

SN - 1061-4036

VL - 48

SP - 624

EP - 633

JO - Nature Genetics

JF - Nature Genetics

IS - 6

ER -

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

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