Polygenic Risk Score Modifies the Association of HbA1c with Hearing Loss in Middle-Aged and Older Chinese: the Dongfeng-Tongji Cohort

Objective: Evidence regarding the modifying effect of polygenic risk score (PRS) on the association between glycemic traits and hearing loss (HL) was lacking. We aimed to examine whether these association can be influenced by genetic susceptibility. Research Design and Methods: The cross-sectional study included 13275 participants aged 64.9 years from the Dongfeng-Tongji cohort. HL was defined according to a pure tone average > 25 dB in the better ear and further classified by severity. Prediabetes and type 2 diabetes (T2D) were defined based on the 2013 criteria from the American Diabetes Association. A PRS was derived from 37 single nucleotide polymorphisms associated with HL. Multivariable logistic regression models were fitted to estimate the associations of PRS and glycemic traits with HL and its severity. Results: Elevated fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), and T2D were positively associated with higher HL risks and its severity, with odds ratios (ORs) ranging from 1.04 (1.00, 1.08) to 1.25 (1.06, 1.46). We also found significant interaction between HbA1c and PRS on risks of overall HL and its severity (P for multiplicative interaction < 0.05), and the effects of HbA1c on HL risks were significant only in high PRS. Additionally, compared to without T2D in the low PRS, T2D was respectively associated with a OR of up to 2.00 and 2.40 for overall HL and moderate to severe HL in the high PRS (P for additive interaction < 0.05). Conclusions: PRS modifies the association of HbA1c with HL prevalence among middle-aged and older Chinese.