“hearing loss” item (because this phenotype generated the most relevant result in the PheWAS conducted) was similarly assessed in both cohorts: WHI – “Hearing loss: Symptom was severe; Symptom was moderate; Symptom was mild; Symptom did not occur”; LLFS – “Respondent able to hear: No; Yes with great difficulty; Yes with little difficulty; Yes without any difficulty”. Both cohorts were stratified for nicotine exposure (more than 100 cigarettes lifetime) and the subsequent analyses were conducted accordingly (exposed vs. unexposed). Because large GWAS cohorts of elderly subjects assessed for hearing loss are limited, we investigated discovery and replication cohorts with different ancestry backgrounds. Previous trans-population studies of CYP2A6 have been conducted successfully9, 10.