MicroRNAs (miRNA) are 21–23-base single-stranded RNA molecules that bind to the end of a messenger RNA (mRNA) and can inhibit protein translation. Human miRNA is usually complementary to a site in the 3′ UTR region of an mRNA. We extracted the 20 base pair flanking sequence on both sides of SNPs in the 3′ UTR region of genes. We search for possible miRNA-binding sites on the 41 base pair DNA sequence for each allele of a SNP using the software miRanda (22), with default parameter values. Using the procedure outlined in Supplementary Figures 3 and 4, we predicted putative miRNA-binding sites for all 677 human miRNAs in the miRBase database (23). We excluded SNPs in miRNA-binding sites that were not conserved in either the mouse or rat homolog sequences. We classified a SNP as affecting miRNA-binding site activity if the miRanda scores for the two alleles differed by ≥16, a value which is equivalent to that of a SNP in the ‘seed’ region of a miRNA-binding site.
