A genome-wide association study of neuroticism in a population-based sample.
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 approximately = 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.
Calboli
Federico C F
FC
Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom. f.calboli@imperial.ac.uk
Tozzi
Federica
F
Galwey
Nicholas W
NW
Antoniades
Athos
A
Mooser
Vincent
V
Preisig
Martin
M
Vollenweider
Peter
P
Waterworth
Dawn
D
Waeber
Gerard
G
Johnson
Michael R
MR
Muglia
Pierandrea
P
Balding
David J
DJ
D000328:Adult; D000368:Aged; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000235:genetics; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D053673:Glypicans / Q000235:genetics; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009497:Neurotic Disorders / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
C120300:GPC6 protein, human; D053673:Glypicans; D008565:Membrane Proteins; C460140:NKAIN2 protein, human; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517376:PDE4D protein, human