Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism

TY - JOUR

T1 - Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism

AU - Luciano, Michelle

AU - Hagenaars, Saskia P.

AU - Davies, Gail

AU - Hill, W. David

AU - Clarke, Toni Kim

AU - Shirali, Masoud

AU - Harris, Sarah E.

AU - Marioni, Riccardo E.

AU - Liewald, David C.

AU - Fawns-Ritchie, Chloe

AU - Adams, Mark J.

AU - Howard, David M.

AU - Lewis, Cathryn M.

AU - Gale, Catharine R.

AU - McIntosh, Andrew M.

AU - Deary, Ian J.

N1 - Funding Information: This research has been conducted using the UK Biobank Resource (application numbers 10279 and 4844). Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006). Ethical approval for the GS:SFHS study was obtained from the Tayside Committee on Medical Research Ethics (05/S1401/89 Tayside Committee on Medical Research Ethics A). We are grateful to all the families who took part, the general practitioners and the Scottish School of Primary Care for their help in recruiting them, and the whole Generation Scotland team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, Publisher Copyright: © 2017 The Author(s).

PY - 2018/1

Y1 - 2018/1

N2 - Neuroticism is a relatively stable personality trait characterized by negative emotionality (for example, worry and guilt) 1 ; heritability estimated from twin studies ranges from 30 to 50% 2, and SNP-based heritability ranges from 6 to 15% 3-6 . Increased neuroticism is associated with poorer mental and physical health 7,8, translating to high economic burden 9 . Genome-wide association studies (GWAS) of neuroticism have identified up to 11 associated genetic loci 3,4 . Here we report 116 significant independent loci from a GWAS of neuroticism in 329,821 UK Biobank participants; 15 of these loci replicated at P < 0.00045 in an unrelated cohort (N = 122,867). Genetic signals were enriched in neuronal genesis and differentiation pathways, and substantial genetic correlations were found between neuroticism and depressive symptoms (r g = 0.82, standard error (s.e.) = 0.03), major depressive disorder (MDD; r g = 0.69, s.e. = 0.07) and subjective well-being (r g = -0.68, s.e. = 0.03) alongside other mental health traits. These discoveries significantly advance understanding of neuroticism and its association with MDD.

AB - Neuroticism is a relatively stable personality trait characterized by negative emotionality (for example, worry and guilt) 1 ; heritability estimated from twin studies ranges from 30 to 50% 2, and SNP-based heritability ranges from 6 to 15% 3-6 . Increased neuroticism is associated with poorer mental and physical health 7,8, translating to high economic burden 9 . Genome-wide association studies (GWAS) of neuroticism have identified up to 11 associated genetic loci 3,4 . Here we report 116 significant independent loci from a GWAS of neuroticism in 329,821 UK Biobank participants; 15 of these loci replicated at P < 0.00045 in an unrelated cohort (N = 122,867). Genetic signals were enriched in neuronal genesis and differentiation pathways, and substantial genetic correlations were found between neuroticism and depressive symptoms (r g = 0.82, standard error (s.e.) = 0.03), major depressive disorder (MDD; r g = 0.69, s.e. = 0.07) and subjective well-being (r g = -0.68, s.e. = 0.03) alongside other mental health traits. These discoveries significantly advance understanding of neuroticism and its association with MDD.

KW - Genetic association study

KW - Psychology

UR - https://www.scopus.com/pages/publications/85038405682

U2 - 10.1038/s41588-017-0013-8

DO - 10.1038/s41588-017-0013-8

M3 - Article

C2 - 29255261

AN - SCOPUS:85038405682

SN - 1061-4036

VL - 50

SP - 6

EP - 11

JO - Nature Genetics

JF - Nature Genetics

ER -