Enrichment control and assessment of SNP novelty

SNPs within the MHC region (defined as chr6: 25,119,106 - 33,854,733) and APOE gene (chr19:44,000,000-47,000,000) were excluded from the analyses due to known association to AD (Lambert et al., 2010; Scheltens et al., 2016) or a very complex LD structure (de Bakker and Raychaudhuri, 2012). For the meta-analysis, we used a modified random effect (RE2) p-value and the GWAS p-value, i.e., p_{meta-analysis} < 5 × 10⁻⁸ and 5 × 10⁻⁸ < p_GWAS-SNP < 0.05 cutoff to identify the novel, previously unidentified shared SNPs between two traits in their original GWAS.

To assess their novelty, we examined our identified loci in previously reported GWAS associations in the National Human Genome Research Institute (NHGRI-EBI) GWAS Catalog (Sollis et al., 2023). We further identified if the gene was novel to any of our traits based on the traits reported in the GWAS Catalog.