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

Aysu Okbay; BML Baselmans; JE De Neve; P Turley; MG Nivard; MA Fontana; SFW Meddens; RK Linner; CA Rietveld; J Derringer; J Gratten; JJ Lee; JZ Liu; R de Vlaming; TS Ahluwalia; J Buchwald; A Cavadino; AC Frazier-Wood; NA Furlotte; V Garfield; MH Geisel; JR Gonzalez; S Haitjema; R Karlsson; Sander Laan; KH Ladwig; J Lahti; Sven van der Lee; PA Lind; T Liu; L Matteson; E Mihailov; MB Miller; CC Minica; IM (Ilja) Nolte; D Mook-Kanamori; PJ van der Most; C Oldmeadow; Y Qian; O Raitakari; R Rawal; A Realo; R Rueedi; B Schmidt; AV Smith; E Stergiakouli; T Tanaka; K Taylor; J Wedenoja; J Wellmann; HJ Westra; SM Willems; W Zhao; Najaf Amin; A Bakshi; PA Boyle; S Cherney; SR Cox; G Davies; OSP Davis; J Ding; Nese Direk; P Eibich; RT Emeny; G Fatemifar; JD Faul; L Ferrucci; A Forstner; C Gieger; R Gupta; TB Harris; JM Harris; EG Holliday; JJ (Jouke Jan) Hottenga; PL De Jager; MA Kaakinen; E Kajantie; V Karhunen; I Kolcic; M Kumari; LJ (Lenore) Launer; L Franke; R Li-Gao; M Koini; A Loukola; P Marques-Vidal; GW Montgomery; MA Mosing; L Paternoster; A Pattie; KE Petrovic; L Pulkki-Raback; L Quaye; K Raikkonen; I Rudan; RJ Scott; JA Smith; AR Sutin; M Trzaskowski; AE Vinkhuyzen; L Yu; D Zabaneh; JR Attia; DA Bennett; K Berger; L Bertram; DI Boomsma; H Snieder; SC Chang; F Cucca; IJ Deary; Cornelia Duijn; JG Eriksson; U Bultmann; EJC de Geus; PJF Groenen; V Gudnason; T Hansen; CA Hartman; CMA Haworth; C Hayward; AC Heath; DA Hinds; E Hypponen; WG Iacono; MR Jarvelin; KH Jockel; J Kaprio; SLR Kardia; L Keltikangas-Jarvinen; P Kraft; LD Kubzansky; T Lehtimaki; PKE Magnusson; NG Martin; M McGue; A Metspalu; M Mills; R de Mutsert; AJ (A.) Oldehinkel; G Pasterkamp; NL Pedersen; R Plomin; O Polasek; C Power; SS Rich; FR Rosendaal; HM den Ruijter; D Schlessinger; Heléna Schmidt; R Svento; R Schmidt; BZ Alizadeh; TIA Sorensen; TD Spector; A Steptoe; A Terracciano; AR Thurik; NJ Timpson; Henning Tiemeier; André Uitterlinden; P Vollenweider; GG Wagner; DR Weir; Jiaqi Yang; DC Conley; GD Smith; Bert Hofman; M Johannesson; DI Laibson; SE Medland; MN Meyer; JK Pickrell; T Esko; RF Krueger; JP Beauchamp; PD Koellinger; DJ Benjamin; MC Bartels; D Cesarini

doi:10.1038/ng.3552

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

Aysu Okbay, BML Baselmans, JE De Neve, P Turley, MG Nivard, MA Fontana, SFW Meddens, RK Linner, CA Rietveld, J Derringer, J Gratten, JJ Lee, JZ Liu, R de Vlaming, TS Ahluwalia, J Buchwald, A Cavadino, AC Frazier-Wood, NA Furlotte, V GarfieldMH Geisel, JR Gonzalez, S Haitjema, R Karlsson, Sander Laan, KH Ladwig, J Lahti, Sven van der Lee, PA Lind, T Liu, L Matteson, E Mihailov, MB Miller, CC Minica, IM (Ilja) Nolte, D Mook-Kanamori, PJ van der Most, C Oldmeadow, Y Qian, O Raitakari, R Rawal, A Realo, R Rueedi, B Schmidt, AV Smith, E Stergiakouli, T Tanaka, K Taylor, J Wedenoja, J Wellmann, HJ Westra, SM Willems, W Zhao, Najaf Amin, A Bakshi, PA Boyle, S Cherney, SR Cox, G Davies, OSP Davis, J Ding, Nese Direk, P Eibich, RT Emeny, G Fatemifar, JD Faul, L Ferrucci, A Forstner, C Gieger, R Gupta, TB Harris, JM Harris, EG Holliday, JJ (Jouke Jan) Hottenga, PL De Jager, MA Kaakinen, E Kajantie, V Karhunen, I Kolcic, M Kumari, LJ (Lenore) Launer, L Franke, R Li-Gao, M Koini, A Loukola, P Marques-Vidal, GW Montgomery, MA Mosing, L Paternoster, A Pattie, KE Petrovic, L Pulkki-Raback, L Quaye, K Raikkonen, I Rudan, RJ Scott, JA Smith, AR Sutin, M Trzaskowski, AE Vinkhuyzen, L Yu, D Zabaneh, JR Attia, DA Bennett, K Berger, L Bertram, DI Boomsma, H Snieder, SC Chang, F Cucca, IJ Deary, Cornelia Duijn, JG Eriksson, U Bultmann, EJC de Geus, PJF Groenen, V Gudnason, T Hansen, CA Hartman, CMA Haworth, C Hayward, AC Heath, DA Hinds, E Hypponen, WG Iacono, MR Jarvelin, KH Jockel, J Kaprio, SLR Kardia, L Keltikangas-Jarvinen, P Kraft, LD Kubzansky, T Lehtimaki, PKE Magnusson, NG Martin, M McGue, A Metspalu, M Mills, R de Mutsert, AJ (A.) Oldehinkel, G Pasterkamp, NL Pedersen, R Plomin, O Polasek, C Power, SS Rich, FR Rosendaal, HM den Ruijter, D Schlessinger, Heléna Schmidt, R Svento, R Schmidt, BZ Alizadeh, TIA Sorensen, TD Spector, A Steptoe, A Terracciano, AR Thurik, NJ Timpson, Henning Tiemeier, André Uitterlinden, P Vollenweider, GG Wagner, DR Weir, Jiaqi Yang, DC Conley, GD Smith, Bert Hofman, M Johannesson, DI Laibson, SE Medland, MN Meyer, JK Pickrell, T Esko, RF Krueger, JP Beauchamp, PD Koellinger, DJ Benjamin, MC Bartels, D Cesarini

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

656 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 (vertical bar(p) over cap vertical bar approximate to 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	10
Journal	Nature Genetics
Volume	48
Issue number	6
DOIs	https://doi.org/10.1038/ng.3552
Publication status	Published - 2016

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EMC NIHES-04-55-01
EMC ONWAR-01-58-02

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10.1038/ng.3552

http://hdl.handle.net/1765/96418

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Okbay, A., Baselmans, BML., De Neve, JE., Turley, P., Nivard, MG., Fontana, MA., Meddens, SFW., Linner, 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., ... 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

@article{b2323d9c8034401c90f44529aab359a8,

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 (vertical bar(p) over cap vertical bar approximate to 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 BML Baselmans and {De Neve}, JE and P Turley and MG Nivard and MA Fontana and SFW Meddens and RK Linner and CA Rietveld and J Derringer and J Gratten and JJ Lee and JZ Liu and {de Vlaming}, R and TS Ahluwalia and J Buchwald and A Cavadino and AC Frazier-Wood and NA Furlotte and V Garfield and MH Geisel and JR Gonzalez and S Haitjema and R Karlsson and Sander Laan and KH Ladwig and J Lahti and {van der Lee}, Sven and PA Lind and T Liu and L Matteson and E Mihailov and MB Miller and CC Minica and Nolte, {IM (Ilja)} and D Mook-Kanamori and {van der Most}, PJ and C Oldmeadow and Y Qian and O Raitakari and R Rawal and A Realo and R Rueedi and B Schmidt and AV Smith and E Stergiakouli and T Tanaka and K Taylor and J Wedenoja and J Wellmann and HJ Westra and SM Willems and W Zhao and Najaf Amin and A Bakshi and PA Boyle and S Cherney and SR Cox and G Davies and OSP Davis and J Ding and Nese Direk and P Eibich and RT Emeny and G Fatemifar and JD Faul and L Ferrucci and A Forstner and C Gieger and R Gupta and TB Harris and JM Harris and EG Holliday and Hottenga, {JJ (Jouke Jan)} and {De Jager}, PL and MA Kaakinen and E Kajantie and V Karhunen and I Kolcic and M Kumari and Launer, {LJ (Lenore)} and L Franke and R Li-Gao and M Koini and A Loukola and P Marques-Vidal and GW Montgomery and MA Mosing and L Paternoster and A Pattie and KE Petrovic and L Pulkki-Raback and L Quaye and K Raikkonen and I Rudan and RJ Scott and JA Smith and AR Sutin and M Trzaskowski and AE Vinkhuyzen and L Yu and D Zabaneh and JR Attia and DA Bennett and K Berger and L Bertram and DI Boomsma and H Snieder and SC Chang and F Cucca and IJ Deary and Cornelia Duijn and JG Eriksson and U Bultmann and {de Geus}, EJC and PJF Groenen and V Gudnason and T Hansen and CA Hartman and CMA Haworth and C Hayward and AC Heath and DA Hinds and E Hypponen and WG Iacono and MR Jarvelin and KH Jockel and J Kaprio and SLR Kardia and L Keltikangas-Jarvinen and P Kraft and LD Kubzansky and T Lehtimaki and PKE Magnusson and NG Martin and M McGue and A Metspalu and M Mills and {de Mutsert}, R and Oldehinkel, {AJ (A.)} and G Pasterkamp and NL Pedersen and R Plomin and O Polasek and C Power and SS Rich and FR Rosendaal and {den Ruijter}, HM and D Schlessinger and Hel{\'e}na Schmidt and R Svento and R Schmidt and BZ Alizadeh and TIA Sorensen and TD Spector and A Steptoe and A Terracciano and AR Thurik and NJ Timpson and Henning Tiemeier and Andr{\'e} Uitterlinden and P Vollenweider and GG Wagner and DR Weir and Jiaqi Yang and DC Conley and GD Smith and Bert Hofman and M Johannesson and DI Laibson and SE Medland and MN Meyer and JK Pickrell and T Esko and RF Krueger and JP Beauchamp and PD Koellinger and DJ Benjamin and MC Bartels and D Cesarini",

year = "2016",

doi = "10.1038/ng.3552",

language = "English",

volume = "48",

pages = "624--633",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "6",

}

Okbay, A, Baselmans, BML, De Neve, JE, Turley, P, Nivard, MG, Fontana, MA, Meddens, SFW, Linner, 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, Laan, S, Ladwig, KH, Lahti, J, van der Lee, S, 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, Taylor, K, Wedenoja, J, Wellmann, J, Westra, HJ, Willems, SM, Zhao, W, 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-Raback, L, Quaye, L, Raikkonen, K, Rudan, I, Scott, RJ, Smith, JA, Sutin, AR, Trzaskowski, M, Vinkhuyzen, AE, Yu, L, Zabaneh, D, Attia, JR, Bennett, DA, Berger, K, Bertram, L, Boomsma, DI, Snieder, H, Chang, SC, Cucca, F, Deary, IJ, Duijn, C, Eriksson, JG, Bultmann, U, de Geus, EJC, Groenen, PJF, Gudnason, V, Hansen, T, Hartman, CA, Haworth, CMA, Hayward, C, Heath, AC, Hinds, DA, Hypponen, E, Iacono, WG, Jarvelin, MR, Jockel, KH, Kaprio, J, Kardia, SLR, Keltikangas-Jarvinen, L, Kraft, P, Kubzansky, LD, Lehtimaki, 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, Sorensen, TIA, Spector, TD, Steptoe, A, Terracciano, A, Thurik, AR, Timpson, NJ, Tiemeier, H, Uitterlinden, A, Vollenweider, P, Wagner, GG, Weir, DR, Yang, J, Conley, DC, Smith, GD, Hofman, B, Johannesson, M, Laibson, DI, Medland, SE, Meyer, MN, Pickrell, JK, Esko, T, Krueger, RF, Beauchamp, JP, Koellinger, PD, Benjamin, DJ, Bartels, MC & 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

TY - JOUR

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

AU - Okbay, Aysu

AU - Baselmans, BML

AU - De Neve, JE

AU - Turley, P

AU - Nivard, MG

AU - Fontana, MA

AU - Meddens, SFW

AU - Linner, RK

AU - Rietveld, CA

AU - Derringer, J

AU - Gratten, J

AU - Lee, JJ

AU - Liu, JZ

AU - de Vlaming, R

AU - Ahluwalia, TS

AU - Buchwald, J

AU - Cavadino, A

AU - Frazier-Wood, AC

AU - Furlotte, NA

AU - Garfield, V

AU - Geisel, MH

AU - Gonzalez, JR

AU - Haitjema, S

AU - Karlsson, R

AU - Laan, Sander

AU - Ladwig, KH

AU - Lahti, J

AU - van der Lee, Sven

AU - Lind, PA

AU - Liu, T

AU - Matteson, L

AU - Mihailov, E

AU - Miller, MB

AU - Minica, CC

AU - Nolte, IM (Ilja)

AU - Mook-Kanamori, D

AU - van der Most, PJ

AU - Oldmeadow, C

AU - Qian, Y

AU - Raitakari, O

AU - Rawal, R

AU - Realo, A

AU - Rueedi, R

AU - Schmidt, B

AU - Smith, AV

AU - Stergiakouli, E

AU - Tanaka, T

AU - Taylor, K

AU - Wedenoja, J

AU - Wellmann, J

AU - Westra, HJ

AU - Willems, SM

AU - Zhao, W

AU - Amin, Najaf

AU - Bakshi, A

AU - Boyle, PA

AU - Cherney, S

AU - Cox, SR

AU - Davies, G

AU - Davis, OSP

AU - Ding, J

AU - Direk, Nese

AU - Eibich, P

AU - Emeny, RT

AU - Fatemifar, G

AU - Faul, JD

AU - Ferrucci, L

AU - Forstner, A

AU - Gieger, C

AU - Gupta, R

AU - Harris, TB

AU - Harris, JM

AU - Holliday, EG

AU - Hottenga, JJ (Jouke Jan)

AU - De Jager, PL

AU - Kaakinen, MA

AU - Kajantie, E

AU - Karhunen, V

AU - Kolcic, I

AU - Kumari, M

AU - Launer, LJ (Lenore)

AU - Franke, L

AU - Li-Gao, R

AU - Koini, M

AU - Loukola, A

AU - Marques-Vidal, P

AU - Montgomery, GW

AU - Mosing, MA

AU - Paternoster, L

AU - Pattie, A

AU - Petrovic, KE

AU - Pulkki-Raback, L

AU - Quaye, L

AU - Raikkonen, K

AU - Rudan, I

AU - Scott, RJ

AU - Smith, JA

AU - Sutin, AR

AU - Trzaskowski, M

AU - Vinkhuyzen, AE

AU - Yu, L

AU - Zabaneh, D

AU - Attia, JR

AU - Bennett, DA

AU - Berger, K

AU - Bertram, L

AU - Boomsma, DI

AU - Snieder, H

AU - Chang, SC

AU - Cucca, F

AU - Deary, IJ

AU - Duijn, Cornelia

AU - Eriksson, JG

AU - Bultmann, U

AU - de Geus, EJC

AU - Groenen, PJF

AU - Gudnason, V

AU - Hansen, T

AU - Hartman, CA

AU - Haworth, CMA

AU - Hayward, C

AU - Heath, AC

AU - Hinds, DA

AU - Hypponen, E

AU - Iacono, WG

AU - Jarvelin, MR

AU - Jockel, KH

AU - Kaprio, J

AU - Kardia, SLR

AU - Keltikangas-Jarvinen, L

AU - Kraft, P

AU - Kubzansky, LD

AU - Lehtimaki, T

AU - Magnusson, PKE

AU - Martin, NG

AU - McGue, M

AU - Metspalu, A

AU - Mills, M

AU - de Mutsert, R

AU - Oldehinkel, AJ (A.)

AU - Pasterkamp, G

AU - Pedersen, NL

AU - Plomin, R

AU - Polasek, O

AU - Power, C

AU - Rich, SS

AU - Rosendaal, FR

AU - den Ruijter, HM

AU - Schlessinger, D

AU - Schmidt, Heléna

AU - Svento, R

AU - Schmidt, R

AU - Alizadeh, BZ

AU - Sorensen, TIA

AU - Spector, TD

AU - Steptoe, A

AU - Terracciano, A

AU - Thurik, AR

AU - Timpson, NJ

AU - Tiemeier, Henning

AU - Uitterlinden, André

AU - Vollenweider, P

AU - Wagner, GG

AU - Weir, DR

AU - Yang, Jiaqi

AU - Conley, DC

AU - Smith, GD

AU - Hofman, Bert

AU - Johannesson, M

AU - Laibson, DI

AU - Medland, SE

AU - Meyer, MN

AU - Pickrell, JK

AU - Esko, T

AU - Krueger, RF

AU - Beauchamp, JP

AU - Koellinger, PD

AU - Benjamin, DJ

AU - Bartels, MC

AU - Cesarini, D

PY - 2016

Y1 - 2016

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 (vertical bar(p) over cap vertical bar approximate to 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 (vertical bar(p) over cap vertical bar approximate to 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

IS - 6

ER -

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

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