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

LifeLines Cohort Study; 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 S 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; Simon R Cox; Gail Davies; Alison Pattie; Igor Rudan; Ian J Deary; Caroline Hayward

doi:10.1038/ng.3552

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

LifeLines Cohort Study, 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 S Ahluwalia, Jadwiga Buchwald, Alana Cavadino, Alexis C Frazier-Wood, Nicholas A FurlotteVictoria 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, Simon R Cox, Gail Davies, Alison Pattie, Igor Rudan, Ian J Deary, Caroline Hayward

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

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 (|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.

Original language	English
Pages (from-to)	624-633
Journal	Nature Genetics
Volume	48
DOIs	https://doi.org/10.1038/ng.3552
Publication status	Published - 18 Apr 2016

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10.1038/ng.3552

RA2661 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2. Main Budget.
Deary, I. (Principal Investigator), Gale, C. (Co-investigator), Holmes, M. (Co-investigator), Logie, P. (Co-investigator), Maclullich, A. (Co-investigator), Porteous, D. (Co-investigator), Seckl, J. (Co-investigator), Starr, J. (Co-investigator), Wardlaw, J. (Co-investigator) & Okely, J. (Researcher)
1/09/13 → 31/08/19
Project: Research

Cite this

LifeLines Cohort Study, 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. S., Buchwald, J., Cavadino, A., Frazier-Wood, A. C., ... Hayward, C. (2016). Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. Nature Genetics, 48, 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 (|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.",

author = "{LifeLines Cohort Study} and 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 Ahluwalia, {Tarunveer S} 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 {van der Laan}, {Sander W} and Karl-Heinz Ladwig 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 Minica, {Camelia C} and Nolte, {Ilja M} 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 Cox, {Simon R} and Gail Davies and Alison Pattie and Igor Rudan and Deary, {Ian J} and Caroline Hayward",

year = "2016",

month = apr,

day = "18",

doi = "10.1038/ng.3552",

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LifeLines Cohort Study, 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, Cox, SR , Davies, G, Pattie, A, Rudan, I , Deary, IJ & Hayward, C 2016, 'Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses', Nature Genetics, vol. 48, pp. 624-633. https://doi.org/10.1038/ng.3552

TY - JOUR

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

AU - LifeLines Cohort Study

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, Tarunveer S

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 - Cox, Simon R

AU - Davies, Gail

AU - Pattie, Alison

AU - Rudan, Igor

AU - Deary, Ian J

AU - Hayward, Caroline

PY - 2016/4/18

Y1 - 2016/4/18

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 (|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.

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 (|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.

U2 - 10.1038/ng.3552

DO - 10.1038/ng.3552

M3 - Article

C2 - 27089181

SN - 1061-4036

VL - 48

SP - 624

EP - 633

JO - Nature Genetics

JF - Nature Genetics

ER -

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

Abstract

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RA2661 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2. Main Budget.

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