Genome-wide association study of neuroticism

This genome-wide study suggests that common variation is not related to neuroticism, and that individual loci have at most a 2% share in its heritability. It is interesting to compare this study with the recent one on height, where a larger number of individuals (~4k) were studied on a smaller number of SNPs (~300k). Are there many SNPs with effects on neuroticism that may have been detected if a larger number of individuals were sampled? I doubt it for two reasons (i) the number of individuals sampled here is not that lower than in the height study, and (ii) neuroticism is a made-up construct that can be imperfectly measured with psychometric testing, while height is a physical reality that can be measured objectively. So, while neuroticism does have a correspondence to brain function, it is much more difficult to discover what it is.

PLoS ONE 5(7): e11504. doi:10.1371/journal.pone.0011504

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

Federico C. F. Calboli et al.

Abstract

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 less than 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.

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