To attain a biological understanding of how rs113288603 affects CYP2A6 function, we investigated its effects on CYP2A6 mRNA expression across human tissues using data from the GTEx consortium (Supplemental Table 4). We observed that rs113288603 * T (protective with respect to hearing loss) is significantly associated with increased CYP2A6 expression in cerebellar hemisphere (p = 9.9 × 10−4; Fig. 2). Comparing rs113288603-expression association with those of rs56113850 * C and rs12461964 * G (the other two alleles identified by NMR GWAS8), we observed that, differently from rs113288603, rs56113850 * C and rs12461964 * G are associated with increased CYP2A6 expression in peripheral tissues (rs56113850: liver p = 1.4 × 10−3, lung p = 5.2 × 10−4, and ovary p = 5.4 × 10−5; rs12461964: liver p = 1.5 × 10−5; Supplemental Table 4).
