We conducted a GWAS of a unidimensional addiction risk factor (addiction-rf) underlying the genetic covariance among PAU, PTU, CUD and OUD by applying GenomicSEM47 to these European ancestry summary statistics. GenomicSEM conducts genome-wide association analyses in two stages. First, a multivariate version of LD score regression is used to estimate the genetic covariance matrix among all GWAS phenotypes, which is then combined with each individual SNP to calculate SNP-specific genetic covariance matrices. Second, these matrices are then used to estimate the SEM using the lavaan package in R52. Variable and unknown extents of sample overlap across contributing GWASs are automatically accounted for in the estimation procedure. The unifactor model fit the data well53 [X2(1) = .017, p = 0.895, CFI = 1, SRMR = 0.002; residual r = 0.51, p = 0.016; Supplemental Figure 1; see also our prior work18 and Online Methods).
