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

    Research output: Contribution to journalArticle

    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 languageEnglish (US)
    Pages (from-to)624-633
    Number of pages10
    JournalNature Genetics
    Volume48
    Issue number6
    DOIs
    StatePublished - Jun 1 2016

    Fingerprint

    Genome
    Depression
    Phenotype
    Genome-Wide Association Study
    Sample Size
    Pancreas
    Central Nervous System
    Joints
    Neuroticism

    ASJC Scopus subject areas

    • Genetics

    Cite this

    Okbay, A., Baselmans, B. M. L., De Neve, J. E., Turley, P., Nivard, M. G., Fontana, M. 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

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

    In: Nature Genetics, Vol. 48, No. 6, 01.06.2016, p. 624-633.

    Research output: Contribution to journalArticle

    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
    Okbay, Aysu ; Baselmans, Bart M L ; De Neve, Jan Emmanuel ; Turley, Patrick ; Nivard, Michel G. ; Fontana, Mark Alan ; Meddens, S. Fleur W ; Linnér, Richard Karlsson ; Rietveld, Cornelius A. ; Derringer, Jaime ; Gratten, Jacob ; Lee, James J. ; Liu, Jimmy Z. ; De Vlaming, Ronald ; SAhluwalia, Tarunveer ; Buchwald, Jadwiga ; Cavadino, Alana ; Frazier-Wood, Alexis C. ; Furlotte, Nicholas A. ; Garfield, Victoria ; Geisel, Marie Henrike ; Gonzalez, Juan R. ; Haitjema, Saskia ; Karlsson, Robert ; Der Laan, Sander Wvan ; Ladwig, Karl Heinz ; Lahti, Jari ; Van Der Lee, Sven J. ; Lind, Penelope A. ; Liu, Tian ; Matteson, Lindsay ; Mihailov, Evelin ; Miller, Michael B. ; CMinica, Camelia ; MNolte, Ilja ; Mook-Kanamori, Dennis ; Van Der Most, Peter J. ; Oldmeadow, Christopher ; Qian, Yong ; Raitakari, Olli ; Rawal, Rajesh ; Realo, Anu ; Rueedi, Rico ; Schmidt, Börge ; Smith, Albert V. ; Stergiakouli, Evie ; Tanaka, Toshiko ; Taylor, Kent ; Wedenoja, Juho ; Wellmann, Juergen ; Westra, Harm Jan ; MWillems, Sara ; Zhao, Wei ; Study, Life Lines Cohort ; Amin, Najaf ; Bakshi, Andrew ; Boyle, Patricia A. ; Cherney, Samantha ; Cox, Simon R. ; Davies, Gail ; Davis, Oliver S P ; Ding, Jun ; Direk, Nese ; Eibich, Peter ; Emeny, Rebecca T. ; Fatemifar, Ghazaleh ; Faul, Jessica D. ; Ferrucci, Luigi ; Forstner, Andreas ; Gieger, Christian ; Gupta, Richa ; Harris, Tamara B. ; Harris, Juliette M. ; Holliday, Elizabeth G. ; Hottenga, Jouke Jan ; De Jager, Philip L. ; Kaakinen, Marika A. ; Kajantie, Eero ; Karhunen, Ville ; Kolcic, Ivana ; Kumari, Meena ; Launer, Lenore J. ; Franke, Lude ; Li-Gao, Ruifang ; Koini, Marisa ; Loukola, Anu ; Marques-Vidal, Pedro ; Montgomery, Grant W. ; Mosing, Miriam A. ; Paternoster, Lavinia ; Pattie, Alison ; Petrovic, Katja E. ; Pulkki-R'back, Laura ; Quaye, Lydia ; R'ikkönen, Katri ; Rudan, Igor ; Scott, Rodney J. ; Smith, Jennifer A. ; Sutin, Angelina R. ; Trzaskowski, Maciej ; Vinkhuyze, Anna E. ; Yu, Lei ; Zabaneh, Delilah ; Attia, John R. ; Bennett, David A. ; Berger, Klaus ; Bertram, Lars ; Boomsma, Dorret I. ; Snieder, Harold ; Chang, Shun Chiao ; Cucca, Francesco ; Deary, Ian J. ; Van Duijn, Cornelia M. ; Eriksson, Johan G. ; Bültmann, Ute ; Geus, Eco J Cde ; Groenen, Patrick J F ; Gudnason, Vilmundur ; Hansen, Torben ; Hartman, Catharine A. ; Haworth, Claire M A ; Hayward, Caroline ; Heath, Andrew C. ; Hinds, David A. ; Hyppönen, Elina ; Iacono, William G. ; J'rvelin, Marjo Riitta ; Jöckel, Karl Heinz ; Kaprio, Jaakko ; Kardia, Sharon L R ; Keltikangas-J'rvinen, Liisa ; Kraft, Peter ; Kubzansky, Laura D. ; Lehtim'ki, Terho ; Magnusson, Patrik K E ; Martin, Nicholas G. ; McGue, Matt ; Metspalu, Andres ; Mills, Melinda ; De Mutsert, Renée ; Oldehinkel, Albertine J. ; Pasterkamp, Gerard ; Pedersen, Nancy L. ; Plomin, Robert ; Polasek, Ozren ; Power, Christine ; Rich, Stephen S. ; Rosendaal, Frits R. ; Den Ruijter, Hester M. ; Schlessinger, David ; Schmidt, Helena ; Svento, Rauli ; Schmidt, Reinhold ; Alizadeh, Behrooz Z. ; SØrensen, Thorkild I A ; DSpector, Tim ; Steptoe, Andrew ; Terracciano, Antonio ; Thurik, A. Roy ; Timpson, Nicholas J. ; Tiemeier, Henning ; Uitterlinden, André G. ; Vollenweider, Peter ; Wagner, Gert G. ; Weir, David R. ; Yang, Jian ; Conley, Dalton C. ; Smith, George Davey ; Hofman, Albert ; Johannesson, Magnus ; Laibson, David I. ; Medland, Sarah E. ; Meyer, Michelle N. ; Pickrell, Joseph K. ; Esko, T'nu ; Krueger, Robert F. ; Beauchamp, Jonathan P. ; Koellinger, Philipp D. ; Benjamin, Daniel J. ; Bartels, Meike ; Cesarini, David. / Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. In: Nature Genetics. 2016 ; Vol. 48, No. 6. pp. 624-633.
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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",
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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

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    AU - Steptoe, Andrew

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    AU - Tiemeier, Henning

    AU - Uitterlinden, André G.

    AU - Vollenweider, Peter

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    AU - Bartels, Meike

    AU - Cesarini, David

    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

    VL - 48

    SP - 624

    EP - 633

    JO - Nature Genetics

    JF - Nature Genetics

    SN - 1061-4036

    IS - 6

    ER -