Genetics
Cross-trait GWAS links hearing loss to HDL and triglyceride genetics, flagging CETP as a candidate druggable target (Mol Genet Genomics 2025)
Original title: Shared genetics between metabolic traits and sensorineural hearing loss: a large-scale genome-wide cross-trait analysis
A genome-wide association study meta-analysis for sensorineural hearing loss (SNHL), the largest to date, was cross-analysed against GWAS data for 14 metabolic traits to test shared genetic architecture. Significant genetic correlations emerged between SNHL and both high triglycerides and low HDL. Cross-trait meta-analysis identified shared loci and pleiotropic genes, with protein-protein interaction networks highlighting TRIOBP, BUD13, APOA5, APOB and CETP as central genes, particularly for the SNHL-HDL and SNHL-triglyceride overlaps. Functional enrichment pointed to auditory and metabolic pathways involving outer hair cells. Druggability analysis flagged SOST and CETP as candidate therapeutic targets for this shared biology. A genetic-correlation study, not a CETP inhibitor trial; the hearing-loss application is novel and unvalidated.
Original abstract
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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.