Chunk #60 — STAR* METHODS — QUANTIFICATION AND STATISTICAL ANALYSIS — Examination of the Impact of Sample Size Imbalance on Genetic Correlations and Genomic SEM Results
M is the total number of SNPs in the genome, μ is a zero vector of length 6, and ∑ is the covariance matrix that accounts for the genetic correlations (rg) among the six disorders (with disease-specific SNP-heritabilities on the diagonal and hihjrg,ij on the off-diagonals). Individual phenotypes were then generated by calculating the sum of betas weighted by the standardized allele dosages (mean 0 and variance 1) with the --score variance-standardize option in PLINK2 v2.00a2LM (Chang et al., 2015) and a noise term drawn from N(0,) for each disorder. Case-control phenotypes were generated by sorting Y in descending order and assigning the top fcase to be cases, where fcase corresponds to the fraction of cases of each disorder in the original GWAS. Association statistics were estimated using logistic regression, assuming an additive effect of alleles. We then matched the reference and the alternate alleles in UKBB to those in the current study and reversed the sign of the effect sizes when necessary. We then performed meta-analysis using ASSET (Bhattacharjee et al., 2012) and estimated m-values as was done in the original analysis. Finally, we compared the distribution of the number of pleiotropic loci across the 100 simulation replicates against
