for rs56113850). Conversely, this same variant, rs113288603, has a strong effect on CYP2A6 brain regulation (particularly in cerebellar hemisphere) and this is protective with respect to hearing loss symptoms. Rs56113850 and rs12461964 seem to provide a minimal contribution to CYP2A6 brain regulation because they appear to be protective with respect to hearing loss symptoms with effect directions opposite with respect to their associations with hepatic expression and serum and urine NMR. Effect directions of the CYP2A6 allele associations with NMR, gene expression, and age-related hearing loss symptoms are summarized in Table 2.Table 2Effect directions of the CYP2A6 allele associations with NMR, gene expression, and age-related hearing loss symptoms.Phenotypers113288603 * Trs56113850 * Crs12461964 * GSourceserum and urinary NMR↓NMR (Genome-wide significance)↑NMR (Genome-wide significance)↑NMR (Genome-wide significance)GWAS (Loukola et al.8; Patel et al.9) CYP2A6 Expression↑Cerebellar hemisphere (Tissue-wide significance)↑Liver (Tissue-wide significance)↑Liver (Tissue-wide significance)GTExAge-related Hearing Loss↓Symptoms (Phenome-wide significance)↑Symptoms (p < 0.1)↑Symptoms (p < 0.1)current study
