Objective: Our study aims to estimate the proportion of the phenotypic variance of Neuroticism and its facet scales that can be attributed to common single-nucleotide polymorphisms (SNPs) in two adult populations from Estonia (EGCUT; N53,292) and the Netherlands (Lifelines; N513,383).

Method: Genomic-relatedness-matrix restricted maximum likelihood (GREML) using genome-wide complex trait analysis (GCTA) software was employed. To build upon previous research, we used self-and informant reports of the 30-facet NEO personality inventories and analyzed both the usual sum scores and the residual facet scores of Neuroticism.

Results: In the EGCUT cohort, the proportion of phenotypic variance explained by the additive effects of common genetic variants in self-and informant-reported Neuroticism domain scores was 15.2% (p=.070, SE=.11) and 6.2% (p=.293, SE=.12), respectively. The SNP-based heritability estimates at the level of Neuroticism facet scales differed greatly across cohorts and modes of measurement but were generally higher (a) for self-than for informant reports, and (b) for sum than for residual scores.

Conclusions: Our findings indicate that a large proportion of the heritability of Neuroticism is not captured by additive genetic effects of common SNPs, with some evidence for Gene 3 Environment interaction across cohorts.