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 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; Evie Stergiakouli; Oliver S P Davis; Ghazaleh Fatemifar; Lavinia Paternoster; Claire M A Haworth; Thorkild Sorensen; Nicholas J Timpson; George Davey Smith; Sarah E Medland; 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, Tarunveer S 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, Evie Stergiakouli, Oliver S P Davis, Ghazaleh Fatemifar, Lavinia Paternoster, Claire M A Haworth, Thorkild Sorensen, Nicholas J Timpson, George Davey Smith, Sarah E Medland, LifeLines Cohort Study

Research output: Contribution to journal › Article (Academic Journal) › peer-review

674 Citations (Scopus)

484 Downloads (Pure)

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
Number of pages	13
Journal	Nature Genetics
Volume	48
Issue number	6
Early online date	18 Apr 2016
DOIs	https://doi.org/10.1038/ng.3552
Publication status	Published - Jun 2016

Keywords

Behavioural genetics
Genome-wide association studies

Access to Document

10.1038/ng.3552

Genetic Associations with Subjective Well-Being
This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Nature at http://www.nature.com/ng/journal/v48/n6/full/ng.3552.html. Please refer to any applicable terms of use of the publisher.
Accepted author manuscript, 794 KB

Handle.net

Persistent link

MRC UoB UNITE Unit - Programme 1
Davey Smith, G. (Principal Investigator)
1/06/13 → 31/03/18
Project: Research
MRC UoB UNITE Unit - programme 3
Timpson, N. J. (Principal Investigator) & Timpson, N. J. (Principal Investigator)
1/06/13 → 31/03/18
Project: Research
MRC Population Health Scientist Fellowship
Paternoster, L. (Principal Investigator)
1/10/12 → 1/10/16
Project: Research

Dr Oliver S Davis
- oliver.davisbristol.acuk
- Bristol Population Health Science Institute
- Bristol Medical School (PHS) - Reader in Statistical Genetics
- MRC Integrative Epidemiology Unit
Person: Academic , Member
Professor Claire M A Haworth
- claire.haworthbristol.acuk
- School of Psychological Science - Professor of Behavioural Genetics
- Bristol Population Health Science Institute
- MRC Integrative Epidemiology Unit
- Bristol Neuroscience
Person: Academic , Member
Professor Evangelia Stergiakouli
- E.Stergiakoulibristol.acuk
- Bristol Medical School (PHS) - Professor of Genetic Epidemiology and Public Mental Health
- Bristol Population Health Science Institute
- MRC Integrative Epidemiology Unit
Person: Academic , Member

Cite this

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., 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), 624-633. https://doi.org/10.1038/ng.3552

@article{d0c789cd41f14eeea18b9bc31d106b90,

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.",

keywords = "Behavioural genetics, Genome-wide association studies",

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 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 Evie Stergiakouli and Davis, {Oliver S P} and Ghazaleh Fatemifar and Lavinia Paternoster and Haworth, {Claire M A} and Thorkild Sorensen and Timpson, {Nicholas J} and Smith, {George Davey} and Medland, {Sarah E} and {LifeLines Cohort Study}",

year = "2016",

month = jun,

doi = "10.1038/ng.3552",

language = "English",

volume = "48",

pages = "624--633",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Springer Nature",

number = "6",

}

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, Stergiakouli, E , Davis, OSP, Fatemifar, G, Paternoster, L , Haworth, CMA, Sorensen, T, Timpson, NJ , Smith, GD, Medland, SE & 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. 624-633. 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 - 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 - Stergiakouli, Evie

AU - Davis, Oliver S P

AU - Fatemifar, Ghazaleh

AU - Paternoster, Lavinia

AU - Haworth, Claire M A

AU - Sorensen, Thorkild

AU - Timpson, Nicholas J

AU - Smith, George Davey

AU - Medland, Sarah E

AU - LifeLines Cohort Study

PY - 2016/6

Y1 - 2016/6

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.

KW - Behavioural genetics

KW - Genome-wide association studies

U2 - 10.1038/ng.3552

DO - 10.1038/ng.3552

M3 - Article (Academic Journal)

C2 - 27089181

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

Abstract

Keywords

Access to Document

Handle.net

Fingerprint

Projects

MRC UoB UNITE Unit - Programme 1

MRC UoB UNITE Unit - programme 3

MRC Population Health Scientist Fellowship

Profiles

Dr Oliver S Davis

Professor Claire M A Haworth

Professor Evangelia Stergiakouli

Cite this