Common SNPs explain some of the variation in the personality dimensions of neuroticism and extraversion.
paper
Cited
Public
- Authors
- Vinkhuyzen, A A E; Pedersen, N L; Yang, J; Lee, S H; Magnusson, P K E; Iacono, W G; McGue, M; Madden, P A F; Heath, A C; Luciano, M; Payton, A; Horan, M; Ollier, W; Pendleton, N; Deary, I J; Montgomery, G W; Martin, N G; Visscher, P M; Wray, N R
- Year
- 2012
- Journal
- Translational psychiatry
- PMID
- 22832902
- DOI
- 10.1038/tp.2012.27
- PMCID
- PMC3337075
The personality traits of neuroticism and extraversion are predictive of a number of social and behavioural outcomes and psychiatric disorders. Twin and family studies have reported moderate heritability estimates for both traits. Few associations have been reported between genetic variants and neuroticism/extraversion, but hardly any have been replicated. Moreover, the ones that have been replicated explain only a small proportion of the heritability (<~2%). Using genome-wide single-nucleotide polymorphism (SNP) data from ~12,000 unrelated individuals we estimated the proportion of phenotypic variance explained by variants in linkage disequilibrium with common SNPs as 0.06 (s.e. = 0.03) for neuroticism and 0.12 (s.e. = 0.03) for extraversion. In an additional series of analyses in a family-based sample, we show that while for both traits ~45% of the phenotypic variance can be explained by pedigree data (that is, expected genetic similarity) one third of this can be explained by SNP data (that is, realized genetic similarity). A part of the so-called 'missing heritability' has now been accounted for, but some of the reported heritability is still unexplained. Possible explanations for the remaining missing heritability are that: (i) rare variants that are not captured by common SNPs on current genotype platforms make a major contribution; and/ or (ii) the estimates of narrow sense heritability from twin and family studies are biased upwards, for example, by not properly accounting for nonadditive genetic factors and/or (common) environmental factors.
Proportion of variance explained by autosomal single-nucleotide polymorphisms (SNPs) for neuroticism (dark blue) and extraversion (light blue). Notes: all individuals included in the analyses have a pair-wise genetic similarity <0.025 except for the * marked in which no cutoff was made; the first 20 principal components (PC) were included as fixed effects in the model, except for the *** marked; error bars represent s.e.; PC; SNPs; UK and USA.**analyses based on 162 056 SNPs that were in common between all study cohorts; adjusted: estimate adjusted for imprecise LD between genotyped SNPs and causal variants for causal variants within the allelic frequency spectrum as genotyped SNPs, using the regression coefficient Ξ² from equation: (assuming c=0), where Ajk is the variance of the off-diagonal elements of the genetic similarity matrix, N is the number of SNPs used to calculate Ajk. The value of c depends on the minor allele frequency of the causal variants.44 Further details and statistics are provided in Supplementary Table S2. Abbreviations: SNPs, single-nucleotide polymorphisms; UK, United Kingdom; USA, United States of America.
Variance explained by each chromosome for neuroticism (a) and extraversion (b). Notes: equation corresponding to the linear regression line for neuroticism: y=8E-06x +0.0017 and extraversion: y=4E-05x +0.0011, where y is the variance explained by each of the chromosomes and x is the total length of the chromosome in mega bases (Mb); R2 corresponding to the regression equation for neuroticism: 0.0202 (P=0.460) and extraversion: 0.203 (P=0.035).
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