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; Tarun Veer Singh Ahluwalia; Jadwiga Buchwald; Alana Cavadino; Alexis C Frazier-Wood; Nicholas A Furlotte; Victoria Garfield; 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; Ute Bültmann; Torben Hansen; Thorkild I A Sørensen; LifeLines Cohort Study

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, Tarun Veer Singh Ahluwalia, Jadwiga Buchwald, Alana Cavadino, Alexis C Frazier-Wood, Nicholas A Furlotte, Victoria GarfieldMarie 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, Ute Bültmann, Torben Hansen, Thorkild I A Sørensen, LifeLines Cohort Study

Department of Public Health

392 Citations (Scopus)

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
Journal	Nature Genetics
Volume	48
Issue number	6
Pages (from-to)	624-33
Number of pages	10
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.3552
Publication status	Published - 1 Jun 2016

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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., Ahluwalia, T. V. S., Buchwald, J., Cavadino, A., Frazier-Wood, A. C., Furlotte, N. A., ... LifeLines Cohort Study (2016). Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. Nature Genetics, 48(6), 624-33. https://doi.org/10.1038/ng.3552

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, TVS, 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, Bültmann, U, Hansen, T , Sørensen, TIA & LifeLines Cohort Study 2016, 'Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses', Nature Genetics, vol. 48, no. 6, pp. 624-33. https://doi.org/10.1038/ng.3552

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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.",

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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 - Ahluwalia, Tarun Veer Singh

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 - van der Laan, Sander W

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 - Minica, Camelia C

AU - Nolte, Ilja M

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 - Bültmann, Ute

AU - Hansen, Torben

AU - Sørensen, Thorkild I A

AU - LifeLines Cohort Study

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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.

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DO - 10.1038/ng.3552

M3 - Journal article

C2 - 27089181

SN - 1061-4036

VL - 48

SP - 624

EP - 633

JO - Nature: New biology

JF - Nature: New biology

IS - 6

ER -

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

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