Shared genetics between metabolic traits and sensorineural hearing loss: a large-scale genome-wide cross-trait analysis.

Sensorineural hearing loss (SNHL) has been epidemiologically linked to metabolic traits, yet their shared genetic basis remains unclear. We performed the largest genome-wide association study (GWAS) meta-analysis for SNHL and analyzed GWAS data from 14 metabolic traits to assess genetic correlations and infer causal relationships. Significant genetic correlations were observed between SNHL and high triglyceride (TG) levels and low high-density lipoprotein (HDL) levels. Cross-trait meta-analyses identified dozens of shared loci and pleiotropic genes, especially between SNHL and HDL or TG. Functional analyses revealed enrichment in pathways related to auditory and metabolic processes, with key involvement of outer hair cells. Protein–protein interaction networks highlighted TRIOBP, BUD13, APOA5, APOB, and CETP as central genes. Druggability analysis suggested SOST and CETP as candidate therapeutic targets. These findings provide novel insights into the genetic architecture of SNHL and its connection with lipid metabolism, highlighting opportunities for developing targeted interventions.