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Hearing-loss and -disorders represent possible mediating pathways in the associations between noise exposures and non-auditory health outcomes. In this context, we questioned whether the noise-obesity associations should consider hearing functions as possible mediators and applied Mendelian randomisation (MR) to investigate causal relationships between body constitution and hearing impairments. We obtained genetic associations from publicly available summary statistics from genome-wide association studies in European adult populations (N= from 210,088 to 360,564) for (i) body constitution: body mass index (BMI), waist circumference (WC) and body fat percentage (BFP), and (ii) hearing loss: sensorineural hearing loss, noise-induced hearing loss, and age-related hearing impairment (ARHI). We employed colocalisation analysis to investigate the genetic associations for BMI and ARHI liability within an FTO locus. We conducted bi-directional MR for the ‘forward’ (from body constitution to hearing) and ‘reverse’ directions. We applied the random-effects inverse variance-weighted method as the main MR method, with additional sensitivity analyses. Colocalisation analysis suggested that BMI and ARHI shared a causal variant at the FTOgene. We did not find robust evidence for causal associations from body constitution to hearing loss and suggested that some associations may be driven by FTO variants. In the reverse analyses, ARHI was negatively associated with BMI [effect size -0.22 (95% CI -0.44 to -0.01)] and BFP [effect size -0.23 (95% CI -0.45 to 0.00)], supporting the notion that ARHI may diminish body constitution. Finally, our data suggest that hearing may have little to no effect on explaining the association between noise exposure and body constitution.

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