We tested 20 principal components for association with BD using logistic regression; seven were significantly associated with phenotype and used in GWAS association analysis (PCs 1-6, 19). In each cohort, we performed logistic regression association tests for BD with imputed marker dosages including 7 principal components to control for population stratification. For all GWAS cohorts, X-chromosome association analyses were conducted separately by sex, and then meta-analyzed across sexes. We also conducted BD1, BD2, and SAB GWAS, retaining only cohorts with at least 30 subtype cases and filtering SNPs for MAF > 0.02. Results were combined across cohorts using an inverse variance-weighted fixed effects meta-analysis 70. We used Plink ‘clumping’ 71,72 to identify an LD-pruned set of discovery GWAS meta-analysis BD-associated variants (P < 0.0001, and distance >500 kb or LD r2 < 0.1, n variants =822) for analysis in the follow-up cohorts. Conditional analyses were conducted within each GWAS cohort and meta-analyzed as above.
