Abstract
Personality traits have been shown to be associated with longevity and healthy aging. In order to discover novel genetic modifiers associated with personality traits as related with longevity, we performed a genome-wide association study (GWAS) on personality factors assessed by NEO-five-factor inventory in individuals enrolled in the Long Life Family Study (LLFS), a study of 583 families (N up to 4595) with clustering for longevity in the United States and Denmark. Three SNPs, in almost perfect LD, associated with agreeableness reached genome-wide significance (p < 10−8) and replicated in an additional sample of 1279 LLFS subjects, although one (rs9650241) failed to replicate and the other two were not available in two independent replication cohorts, the Baltimore Longitudinal Study of Aging and the New England Centenarian Study. Based on 10,000,000 permutations, the empirical p-value of 2 × 10−7 was observed for the genome-wide significant SNPs. Seventeen SNPs that reached marginal statistical significance in the two previous GWASs (p-value <10−4 and 10−5), were also marginally significantly associated in this study (p-value <0.05), although none of the associations passed the Bonferroni correction. In addition, we tested age-by-SNP interactions and found some significant associations. Since scores of personality traits in LLFS subjects change in the oldest ages, and genetic factors outweigh environmental factors to achieve extreme ages, these age-by-SNP interactions could be a proxy for complex gene–gene interactions affecting personality traits and longevity.
Highlights
Personality traits have been shown to be associated with important health outcomes and longevity (Terracciano et al, 2008)
Heritability estimates of agreeableness, conscientiousness, extraversion, neuroticism, and openness assessed by the NEO-five-factor inventory (NEO-FFI) in 6148 Sardinians ranged from 17 to 33% (Pilia et al, 2006), and a recent genome-wide association study (GWAS) and meta-analysis identified many genetic variants associated with personality traits, just a few reached levels of genome-wide significance (Terracciano et al, 2010; de Moor et al, 2012)
The top findings (p-value
Summary
Personality traits have been shown to be associated with important health outcomes and longevity (Terracciano et al, 2008). Heritability estimates of agreeableness, conscientiousness, extraversion, neuroticism, and openness assessed by the NEO-FFI in 6148 Sardinians ranged from 17 to 33% (Pilia et al, 2006), and a recent genome-wide association study (GWAS) and meta-analysis identified many genetic variants associated with personality traits, just a few reached levels of genome-wide significance (Terracciano et al, 2010; de Moor et al, 2012). This enrichment of associations suggests that personality traits are likely influenced by many genes in a complex manner, each with small effects
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