SNP heritability (h2SNP) was estimated by LD score regression74 using summary statistics from the GWAS of CUD and pre-computed LD scores (available on https://github.com/bulik/ldsc). The SNP heritability was calculated on the liability scale using a prevalence of CUD of 1% in the population. The h2SNP estimated by LD score regression was inaccurate as the ratio between the estimated h2SNP and the standard error was less than four (h2SNP/SE=2,86). Therefore, the h2SNP was also estimated using GCTA75. A genomic relationship matrix (GRM) between all pairwise combinations of individuals was estimated for each autosome separately and subsequently merged using the GCTA software. The strict best-guess-genotypes (i.e. 4,299,887 SNPs with info score >0.8, missing rate <0.01 and MAF >0.01) from imputation with phase 3 of 1000 genomes were used for GRM estimation. Univariate GREML analyses in GCTA was used to estimate h2SNP on the liability scale, using the combined GRM and the same covariates as in the GWAS.
