Assessing Gene-by-Smoking Interactions on Hearing Loss in Japanese Americans: A Candidate Gene Study
The prevalence of hearing loss and cigarette smoking poses major public health concerns. Studies have shown conflicting results between the association of smoking and hearing loss. As a complex, multifactorial disease, the discrepancy may be attributed to genetic modifiers that modify the relationship. Preliminary results using a genome-wide ordered subset analysis (OSA) analyzed Japanese American families and detected six regions on the genome showing evidence for gene-by-smoking interactions: 8q21, 7p21, 11q23, 12q32, 15q26, and 20q13. In this study, a candidate gene approach is used to specifically assess which genes may be driving the signals. A sample of 17 Japanese American families (N = 129) from the Genetics of Non-insulin Dependent Diabetes Mellitus (GENNID) study were selected and genotyped for analysis. Markers within, or close to 19 candidate genes previously implicated for hearing less were tested for interaction using logistic regression models. Generalized estimating equations adjusted for within-family correlations. Six genes were found to be significantly modifying the association between smoking and hearing loss: GNAS, RIPK2, GRLH2, RDX, EYA1, and HOMER2 with GNAS significant after a Bonferroni correction. GNAS, GRHL2, and RDX significantly predicted hearing loss, independent of the effects of aging and smoking. This report provides evidence that the effect of smoking on hearing loss can be dependent on genotype. With a high prevalence of hearing loss and cigarette smoking worldwide and in the U.S, exploring this relationship can be useful for strategies to prevent hearing loss and reduce cigarette usage.