A Genome-Wide Association Study of Neuroticism in a Population-Based Sample

PLoS One

Michael R. Johnson¹  Athos Antoniades²  Federico C. F. Calboli³  David J. Balding³  Peter Vollenweider⁴  Gerard Waeber⁴  Martin Preisig⁵  Nicholas W. Galwey⁶  Pierandrea Muglia⁷  Vincent Mooser⁸  Dawn Waterworth⁸  Federica Tozzi⁹ 

[1] Department of Clinical Neurosciences, Imperial College London, London, United Kingdom;Department of Computer Science, University of Cyprus, Nicosia, Cyprus;Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom;Department of Internal Medicine, University Hospital Center and University of Lausanne, Lausanne, Switzerland;Department of Psychiatry, University Hospital Center and University of Lausanne, Lausanne, Switzerland;Discovery Biometrics Respiratory, GlaxoSmithKline, Greenford, United Kingdom;Discovery Medicine, Neurosciences CEDD, GlaxoSmithKline R&D, Verona, Italy;Genetics Division, Drug Discovery, GlaxoSmithKline R&D, Upper Merion, Pennsylvania, United States of America;Genetics Division, Drug Discovery, GlaxoSmithKline R&D, Verona, Italy

关键词: Molecular genetics;    Variant genotypes;    Genome-wide association studies;    Heredity;    Genomic signal processing;    Questionnaires;    Dementia;    Personality;   

DOI  :  10.1371/journal.pone.0011504

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

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. After Quality Control, we analysed 430,000 autosomal SNPs together with an additional 1.2 million SNPs imputed with high quality from the Hap Map CEU samples. We found a very small effect of population stratification, corrected using one principal component, and some cryptic kinship that required no correction. NKAIN2 showed suggestive evidence of association with neuroticism as a main effect (p<10−6) and GPC6 showed suggestive evidence for interaction with age (p≈10−7). We found support for one previously-reported association (PDE4D), but failed to replicate other recent reports. These results suggest common SNP variation does not strongly influence neuroticism. Our study was powered to detect almost all SNPs explaining at least 2% of heritability, and so our results effectively exclude the existence of loci having a major effect on neuroticism.

【 授权许可】

CC BY