Functional annotation of SNPs implicated in the meta-analysis was performed using FUMA24 (see URLs). We selected all candidate SNPs in associated genomic loci having an r2≧0.6 with one of the independent significant SNPs (see above), a suggestive P-value (P<1e-5) and a MAF>0.0001 for annotations. Predicted functional consequences for these SNPs were obtained by matching SNPs’ chromosome, base-pair position, and reference and alternate alleles to databases containing known functional annotations, including ANNOVAR43 categories, Combined Annotation Dependent Depletion (CADD) scores23, RegulomeDB44 (RDB) scores, and chromatin states45,46. ANNOVAR categories identify the SNP’s genic position (e.g. intron, exon, intergenic) and associated function. CADD scores predict how deleterious the effect of a SNP is likely to be for a protein structure/function, with higher scores referring to higher deleteriousness. A CADD score above 12.37 is the threshold to be potentially pathogenic23. The RegulomeDB score is a categorical score based on information from expression quantitative trait loci (eQTLs) and chromatin marks, ranging from 1a to 7 with lower scores indicating an increased likelihood of having a regulatory function. Scores are as follows: 1a=eQTL + Transcription Factor (TF)
