Genome-wide analysis of over 106,000 individuals identifies 9 neuroticism-associated loci (original) (raw)
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A genome-wide association study of neuroticism in a population-based sample
2010
Neuroticism is a moderately heritable personality trait considered to be a risk factor for developing major depression, anxiety disorders and dementia. We performed a genome-wide association study in 2,235 participants drawn from a population-based study of neuroticism, making this the largest association study for neuroticism to date. Neuroticism was measured by the Eysenck Personality Questionnaire.
A whole genome association study of neuroticism using DNA pooling
2007
Abstract We describe a multistage approach to identify single nucleotide polymorphisms (SNPs) associated with neuroticism, a personality trait that shares genetic determinants with major depression and anxiety disorders. Whole genome association with 452 574 SNPs was performed on DNA pools from~ 2000 individuals selected on extremes of neuroticism scores from a cohort of 88 142 people from southwest England. The most significant SNPs were then genotyped on independent samples to replicate findings.
Genetic Underpinnings of Neuroticism: A Replication Study
Journal of Addiction Research & Therapy, 2012
Our sample of 215 unrelated healthy European Caucasian subjects (35% male, age 48.9±16.1) was collected as part of the "Leisure, Lifestyle, and Lifecycle" Project in the province of Alberta, Canada . Presence of a lifetime psychiatric disorders was an exclusion criteria and was assessed through the Composite International Diagnostic Interview (CIDI) . Personality traits were assessed using the NEO-FFI, which is a 60-item short version of the NEO-PI-R (Revised NEO Personality Inventory). This personality assessment measures Abstract Background: Neuroticism, as defined and measured by the NEO Personality Inventory (Neuroticism Extraversion and Openness Personality Inventory), is a core personality trait reflecting an individual's emotional reactivity. High neuroticism is thought to be an important vulnerability factor for various psychiatric disorders in the general population, including substance abuse, depression, anxiety, and psychosis. Recent findings support the hypothesis that genetic factors underlying the neuroticism trait could increase the susceptibility to psychiatric disorders. The current study aimed to replicate genetic associations with high neuroticism previously reported in the literature. Methods: We genotyped four polymorphisms: CNR1 (rs7766029), GABRA2 (rs9291283), GABRA6 (rs3219151) and MAMDC1 (rs7151262) in 215 healthy Caucasian subjects, who completed a short version of the NEO-PI. NEO neuroticism scores of the three genotype groups were compared using ANCOVA, with age as a covariate.
Archives of General Psychiatry, 2008
Classical genetic study designs such as family and twin studies provide evidence for familial aggregation and the magnitude of genetic component. Furthermore, linkage studies map susceptible regions for diseases. Genomic regions that are identified by linkage analyses are likely to contain genes influencing one disorder or including pleiotropic loci and can then be targeted for more extensive gene identification, namely candidate gene association study. Due to the rapid advances in genotyping technology, genome-wide association studies (GWAS) with hundreds of thousands of markers are now becoming popular. The GWAS is a hypothesis free method which densely genotypes SNPs (single nucleotide polymorphism) and CNVs (copy number variations) along the whole genome without prior hypotheses of candidate genes for the diseases. These large scale genetic studies offer great promise to expedite the discovery of the common genetic variants affecting common diseases or traits of interest. In the recent few years, the GWAS has demonstrated to be a successful strategy because there have been multiple successes with the identification of highly compelling candidate genes, such as age-related macular degeneration, body mass index, inflammatory bowel disease, and type 2 diabetes mellitus.
Genome-wide association uncovers shared genetic effects among personality traits and mood states
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2012
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 ¼ 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 ¼ 527-6,032). Suggestive association (P ¼ 8 Â 10 À8 ) of rs1079196 in the FHIT gene was observed with symptoms of anxiety. Other notable associations (P < 6.09 Â 10 À6 ) 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.
Genetic and Phenotypic Stability of Measures of Neuroticism Over 22 Years
Twin Research and Human Genetics, 2007
People meeting diagnostic criteria for anxiety or depressive disorders tend to score high on the personality scale of neuroticism. Studying this dimension of personality can therefore give insights into the etiology of important psychiatric disorders. Neuroticism can be assessed easily via self-report questionnaires in large population samples. We have examined the genetic and phenotypic stability of neuroticism, measured up to 4 times over 22 years, on different scales, on a data set of 4999 families with over 20,000 individuals completing at least 1 neuroticism questionnaire. The neuroticism scales used were the Eysenck Personality Questionnaire revised (EPQ-R), the EPQ-R shortened form, and the NEO 5 factor inventory personality questionnaire. The estimates of heritability of the individual measures ranged from .26 ± .04 to .36 ± .03. Genetic, environmental, and phenotypic correlations averaged .91, .42, and .57 respectively. Despite the range in heritabilities, a more parsimonio...
Nature genetics, 2017
Personality is influenced by genetic and environmental factors and associated with mental health. However, the underlying genetic determinants are largely unknown. We identified six genetic loci, including five novel loci, significantly associated with personality traits in a meta-analysis of genome-wide association studies (N = 123,132-260,861). Of these genome-wide significant loci, extraversion was associated with variants in WSCD2 and near PCDH15, and neuroticism with variants on chromosome 8p23.1 and in L3MBTL2. We performed a principal component analysis to extract major dimensions underlying genetic variations among five personality traits and six psychiatric disorders (N = 5,422-18,759). The first genetic dimension separated personality traits and psychiatric disorders, except that neuroticism and openness to experience were clustered with the disorders. High genetic correlations were found between extraversion and attention-deficit-hyperactivity disorder (ADHD) and between ...
Nature genetics, 2016
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 n...
Journal of Personality, 2016
Our study aims to estimate the proportion of the phenotypic variance of Neuroticism and its facet scales that can be attributed to common SNPs in two adult populations from Estonia (EGCUT; N = 3,292) and the Netherlands (Lifelines; N = 13,383). Method: Genomic-Relatedness-Matrix Restricted Maximum Likelihood (GREML) using Genome-wide Complex Trait Analysis (GCTA) software was employed. To build upon previous research, we used self- and informant-reports of the 30-facet NEO personality inventories and analyzed both the usual sum scores and the residual facet scores of Neuroticism. Results: In the EGCUT cohort, the proportion of phenotypic variance explained by the additive effects of common genetic variants in self- and informant-reported Neuroticism domain scores was 15.2% (p = .070, SE = .11) and 6.2% (p = .293, SE = .12), respectively. The SNP-based heritability estimates at the level of Neuroticism facet scales differed greatly across cohorts and modes of measurement but were generally higher (a) for self- than for informant-reports, and (b) for sum than for residual scores. Conclusions: Our findings indicate that a large proportion of the heritability of Neuroticism is not captured by additive genetic effects of common SNPs with some evidence for gene-environment interaction across cohorts.