In two large cohorts included in the meta-analysis, the Netherlands Twin Register (NTR, N = 3,599 unrelated individuals) cohort and the QIMR Berghofer Medical Research Institute (QIMR, N= 3,369) adult cohort, Genomic-relatedness-matrix Restricted Maximum Likelihood (GREML) analysis in the GCTA software was applied to estimate the proportion of variance in neuroticism that can be explained by common SNPs.43,50 GCTA analysis was based on best guess genotypes obtained in PLINK using a threshold of a maximum genotype probability >0.70, and additionally filtering on r-squared >0.80. Next, in estimating the GRM matrix in the GCTA software, SNPs with MAF <0.05 were excluded. The additive genetic relationship matrix (GRM) for all individuals in the data sets estimated based on SNPs was used to estimate the proportion of phenotypic variance due to additive genetic variance. Sex, age and population-specific principal components (PCs) were included as covariates.
