The core function of FUMA is the SNP2GENE process (Fig.1) in which SNPs are annotated with their biological functionality and mapped to genes based on positional, eQTL and chromatin interaction information of SNPs. First, based on the provided summary statistics (input format is available in Supplementary Note 1), independent significant SNPs and their surrounding genomic loci are identified by FUMA depending on LD structure, and define lead SNPs and genomic risk loci (Methods). Independent significant SNPs and SNPs that are in LD with the independent significant SNPs are then annotated for functional consequences on gene functions (based on Ensembl genes (build 85) using ANNOVAR12), deleteriousness score (CADD score13), potential regulatory functions (RegulomeDB score14 and 15-core chromatin state predicted by ChromHMM15 for 127 tissue/cell types9,10), effects on gene expression using eQTLs of various tissue types and 3D structure of chromatin interactions with Hi-C data (Methods). In addition, independent significant SNPs and correlated SNPs are also linked to the GWAS catalog1 to provide insight into previously reported associations of the SNPs in the risk loci with a variety of phenotypes.
