After applying similar data quality controls, we conducted within-cohort association analyses using logistic regression and relevant covariates (Methods). We estimated the proportion of variance attributable to the measured common variants (SNP-heritability, h2SNP) to be ~5–15% (based on liability scale, assuming a lifetime risk of 12.5%; Figure 1b, Supplementary Table 6), which is consistent with prior nicotine-related GWAS.13,27 Genetic correlations across sites and ancestries were mostly high and positive (rg>0.51, p<1.56E-02, EUR sites; rg=0.93, p=0.45, AA sites; cross-ancestry rgs=0.74–0.84, p<3.90E-04; Figure 1b, Supplementary Table 6), serving as the basis for ancestry-specific and multi-ancestry meta-analyses, and suggesting that the genetic architecture of TUD is similar across ancestries.
