title: Genome-wide association uncovers shared genetic effects among personality traits and mood states.
abstract: Measures of personality and psychological distress are correlated and exhibit genetic covariance. We conducted univariate genome-wide SNP (~2.5 million) and gene-based association analyses of these traits and examined the overlap in results across traits, including a prediction analysis of mood states using genetic polygenic scores for personality. Measures of neuroticism, extraversion, and symptoms of anxiety, depression, and general psychological distress were collected in eight European cohorts (n ranged 546-1,338; maximum total n = 6,268) whose mean age ranged from 55 to 79 years. Meta-analysis of the cohort results was performed, with follow-up associations of the top SNPs and genes investigated in independent cohorts (n = 527-6,032). Suggestive association (P = 8 × 10(-8)) of rs1079196 in the FHIT gene was observed with symptoms of anxiety. Other notable associations (P < 6.09 × 10(-6)) included SNPs in five genes for neuroticism (LCE3C, POLR3A, LMAN1L, ULK3, SCAMP2), KIAA0802 for extraversion, and NOS1 for general psychological distress. An association between symptoms of depression and rs7582472 (near to MGAT5 and NCKAP5) was replicated in two independent samples, but other replication findings were less consistent. Gene-based tests identified a significant locus on chromosome 15 (spanning five genes) associated with neuroticism which replicated (P < 0.05) in an independent cohort. Support for common genetic effects among personality and mood (particularly neuroticism and depressive symptoms) was found in terms of SNP association overlap and polygenic score prediction. The variance explained by individual SNPs was very small (up to 1%) confirming that there are no moderate/large effects of common SNPs on personality and related traits.
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. michelle.luciano@ed.ac.uk
authors.forename: Michelle
authors.initials: M
authors.lastname: Luciano
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Huffman
authors.forename: Alejandro
authors.initials: A
authors.lastname: Arias-Vásquez
authors.forename: Anna A E
authors.initials: AA
authors.lastname: Vinkhuyzen
authors.forename: Christel M
authors.initials: CM
authors.lastname: Middeldorp
authors.forename: Ina
authors.initials: I
authors.lastname: Giegling
authors.forename: Antony
authors.initials: A
authors.lastname: Payton
authors.forename: Gail
authors.initials: G
authors.lastname: Davies
authors.forename: Lina
authors.initials: L
authors.lastname: Zgaga
authors.forename: Joost
authors.initials: J
authors.lastname: Janzing
authors.forename: Xiayi
authors.initials: X
authors.lastname: Ke
authors.forename: Tessel
authors.initials: T
authors.lastname: Galesloot
authors.forename: Annette M
authors.initials: AM
authors.lastname: Hartmann
authors.forename: William
authors.initials: W
authors.lastname: Ollier
authors.forename: Albert
authors.initials: A
authors.lastname: Tenesa
authors.forename: Caroline
authors.initials: C
authors.lastname: Hayward
authors.forename: Maaike
authors.initials: M
authors.lastname: Verhagen
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.forename: Jouke-Jan
authors.initials: JJ
authors.lastname: Hottenga
authors.forename: Bettina
authors.initials: B
authors.lastname: Konte
authors.forename: John M
authors.initials: JM
authors.lastname: Starr
authors.forename: Veronique
authors.initials: V
authors.lastname: Vitart
authors.forename: Pieter E
authors.initials: PE
authors.lastname: Vos
authors.forename: Pamela A F
authors.initials: PA
authors.lastname: Madden
authors.forename: Gonneke
authors.initials: G
authors.lastname: Willemsen
authors.forename: Heike
authors.initials: H
authors.lastname: Konnerth
authors.forename: Michael A
authors.initials: MA
authors.lastname: Horan
authors.forename: David J
authors.initials: DJ
authors.lastname: Porteous
authors.forename: Harry
authors.initials: H
authors.lastname: Campbell
authors.forename: Sita H
authors.initials: SH
authors.lastname: Vermeulen
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Heath
authors.forename: Alan
authors.initials: A
authors.lastname: Wright
authors.forename: Ozren
authors.initials: O
authors.lastname: Polasek
authors.forename: Sanja B
authors.initials: SB
authors.lastname: Kovacevic
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Hastie
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.forename: Dorret I
authors.initials: DI
authors.lastname: Boomsma
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.forename: Dan
authors.initials: D
authors.lastname: Rujescu
authors.forename: James F
authors.initials: JF
authors.lastname: Wilson
authors.forename: Jan
authors.initials: J
authors.lastname: Buitelaar
authors.forename: Neil
authors.initials: N
authors.lastname: Pendleton
authors.forename: Igor
authors.initials: I
authors.lastname: Rudan
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Deary
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001007:Anxiety / Q000235:genetics; D015331:Cohort Studies; D003863:Depression / Q000235:genetics; D005120:Extraversion, Psychological; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000235:genetics*; D009483:Neuropsychological Tests; D009497:Neurotic Disorders / Q000235:genetics; D010551:Personality / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results; D055815:Young Adult