observed in the LLFS nicotine-unexposed sample (p = 0.524). A difference was observed when considering an interaction with nicotine exposure for the LLFS sample (nicotine-exposed vs. nicotine-unexposed; p = 0.097). Beyond rs113288603, we observed evidence for possible associations of rs56113850 * C and rs12461964 * G (the other two alleles identified by NMR GWAS8) with increased hearing loss symptoms in nicotine-exposed subjects (p = 0.053 and p = 0.089, respectively; Supplemental Table 3).Table 1Association between CYP2A6 rs113288603 and hearing loss symptoms in discovery and replication cohorts (WHI and LLFS, respectively).CohortNicotine StatusNAlleleEffect Allele FrequencyBetaSEPZInteraction PInteraction WHIExposed3401T0.10−0.0180.0045.75 × 10−5 −2.628.67 × 10−3 Unexposed3245−0.0010.0050.8708LLFSExposed20770.09−0.2490.1510.098−1.660.097Unexposed25480.0850.1330.524
