Abstract
BackgroundThis study investigated the relationship between smoking and hearing loss and deafness (HLD) and whether the relationship is modified by genetic variation. Data for these analyses was from the subset of Japanese American families collected as part of the American Diabetes Association Genetics of Non-insulin Dependent Diabetes Mellitus study. Logistic regression with generalized estimating equations assessed the relationship between HLD and smoking. Nonparametric linkage analysis identified genetic regions harboring HLD susceptibility genes and ordered subset analysis was used to identify regions showing evidence for gene-smoking interactions. Genetic variants within these candidate regions were then each tested for interaction with smoking using logistic regression models. ResultsAfter adjusting for age, sex, diabetes status and smoking duration, for each pack of cigarettes smoked per day, risk of HLD increased 4.58 times (odds ratio (OR) = 4.58; 95% Confidence Interval (CI): (1.40,15.03)), and ever smokers were over 5 times more likely than nonsmokers to report HLD (OR = 5.22; 95% CI: (1.24, 22.03)). Suggestive evidence for linkage for HLD was observed in multiple genomic regions (Chromosomes 5p15, 8p23 and 17q21), and additional suggestive regions were identified when considering interactions with smoking status (Chromosomes 7p21, 11q23, 12q32, 15q26, and 20q13) and packs-per-day (Chromosome 8q21). ConclusionsTo our knowledge this was the first report of possible gene-by-smoking interactions in HLD using family data. Additional work, including independent replication, is needed to understand the basis of these findings. HLD are important public health issues and understanding the contributions of genetic and environmental factors may inform public health messages and policies.
Highlights
In the United States, hearing loss is the most common sensory impairment affecting about 1 in every 8 Americans and is the most prevalent sensory disorder in developed countries (Lin et al, 2011a; Uchida et al, 2012)
Family history is significantly associated with hearing loss (Smith et al, 2014; McMahon et al, 2008), and approximately 36% of the variance is attributable to genetic variation (h2 1⁄4 0.36) (Kvestad et al, 2012)
The characteristics of 75 Japanese American individuals in 8 families are presented in Table 1; there was a median of 10 subjects per family with a minimum of 9 subjects and a maximum of 19 subjects per family
Summary
In the United States, hearing loss is the most common sensory impairment affecting about 1 in every 8 Americans and is the most prevalent sensory disorder in developed countries (Lin et al, 2011a; Uchida et al, 2012). Lavinsky and colleagues (Lavinsky et al, 2015) conducted a genome-wide association study (GWAS) and identified NADPHoxidase 3, located on chromosome 6, as a critical gene for susceptibility to hearing loss In another GWAS, Friedman and researchers (Friedman et al, 2009) identified common alleles of GRM7, located on Chromosome 3, that contribute to an individual's susceptibility of developing age-related hearing impairment. This study investigated the relationship between smoking and hearing loss and deafness (HLD) and whether the relationship is modified by genetic variation Data for these analyses was from the subset of Japanese American families collected as part of the American Diabetes Association Genetics of Non-insulin Dependent Diabetes Mellitus study. Nonparametric linkage analysis identified genetic regions harboring HLD susceptibility genes and ordered subset analysis was used to identify regions showing evidence for gene-smoking interactions. HLD are important public health issues and understanding the contributions of genetic and environmental factors may inform public health messages and policies
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