Correlation between SLC39A8 gene and body constitution-related phenotypes and hearing loss: a Mendelian randomization-based study.

Introduction: We examined the role of hearing functions as potential mediators in relationships between noise exposures and abnormal body constitution-related results. Additionally, we employed Mendelian randomization (MR) to explore the causative connections between hearing problems and bodily composition.

Material and methods: Gene connections pertaining to phenotypes of hearing loss and body constitution were obtained from publicly available summary data collected from adult population genome-wide association studies. Colocalization analysis was utilized to scrutinize the genetic associations pertaining to age-related hearing impairment (ARHI) liability and body mass index (BMI) within the SLC39A8 locus. For a comprehensive examination, we employed bi-directional MR encompassing both the 'forward' direction (from the composition of the body to hearing) and the 'reverse' direction.

Results: A common causative variable (rs13107325) for BMI and ARHI at the SLC39A8 locus was supported by colocalization analysis, which revealed that the two diseases shared the variant at the SLC39A8 gene. The forward analyses showed that body fat percentage (BFP) was significantly linked with the risk of ARHI (OR = 0.95 (95% CI: 0.93 to 0.98)) and that waist circumference (WC) was favorably associated with sensorineural hearing loss (SNHL) (OR = 0.83 (95% CI: 0.72 to 0.97)).

Conclusions: We did not find evidence to support a causal relationship between constitution and HL in the reverse MR analysis. Colocalization analysis indicated that the SLC39A8 variant was often the source of high ARHI and BMI risk. In prospective MR, we discovered causal associations between WC and BFP with SNHL and ARHI, respectively. Therefore, our results suggest that lipid metabolic abnormalities leading to adverse health outcome may lead to HL.