For the candidate genes that pass the above screen we extract SNPs from dbSNP and process this list as shown in Figure 1. If a SNP was examined in the GWAS and had a P-value less than the user-specified threshold T1 it is retained. If a SNP was not in the GWAS but was in high LD with a GWAS SNP that had a P-value larger than T1 it is eliminated because we reason that it was adequately evaluated by the GWAS and found to have no association with disease. We then score all retained SNPs for functional significance and apply different minor allele frequency (MAF) filters depending on the functional category of the SNP. These user-specified MAF filters are provided because functionally important SNPs often have lower MAF due to natural selection (6) and we wish to provide extra flexibility to retain functional SNPs below the MAF filter being applied to SNPs without such function. The details of the functional predictions used in this and other pipelines are provided in a separate section below.
