The major source of discrepancy between H-MAGMA and cMAGMA is non-coding variants because promoter and exonic SNPs were assigned to the same genes in both frameworks. We therefore tested how often intronic and intergenic SNPs can be mapped to the nearest genes as predicted by cMAGMA. We found that only 20% of intronic SNPs and 5% of intergenic SNPs interact with nearest genes based on Hi-C (Fig. 1b, Extended Data Fig. 1a, Methods). Because Hi-C based gene mapping cannot capture proximal interactions within 10kb4, we additionally used an eQTL resource from the human DLPFC3, from which we found 56% of intronic SNPs and 76% of intergenic SNPs did not show any association with nearest genes (Extended Data Fig. 1a, Methods). The majority of non-coding SNPs associated with nearest genes showed additional association with distal genes, as 80% of intronic SNPs and 87% of intergenic SNPs showed associations with distal genes (Fig. 1b). These results highlight the importance of using functional genomic evidence in assigning non-coding SNPs to genes.
