that some SNPs may not be functionally related to their assigned gene(s). In addition, SNPs that map to multiple genes in the same pathway can yield spurious pathway association. This issue is particularly important for genes (such as the MHC/HLA genes) that cluster in the genome and belong to the same pathway, because variants in those genomic regions can potentially map to all genes in the pathway. Finally, given the importance of SNP-to-gene mapping for pathway analyses, investigators should be aware that imputation can increase gene coverage by characterizing SNP genotypes that are not directly available in a particular data set. Imputation can be particularly useful for bridging differences in genotyping platforms across cohorts for replication and meta-analysis, and can also enable investigation of rare alleles and copy number variants (CNVs) that are less-represented on standard platforms [38].
