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Genome-wide screen of otosclerosis in population biobanks: 27 loci and shared associations with skeletal structure
- Source :
- Nature Communications. 14
- Publication Year :
- 2023
- Publisher :
- Springer Science and Business Media LLC, 2023.
-
Abstract
- Otosclerosis is one of the most common causes of conductive hearing loss, affecting 0.3% of the population. It typically presents in adulthood and half of the patients have a positive family history. The pathophysiology of otosclerosis is poorly understood. A previous genome-wide association study (GWAS) identified a single association locus in an intronic region of RELN. Here, we report a meta-analysis of GWAS studies of otosclerosis in three population-based biobanks comprising 3504 cases and 861,198 controls. We identify 23 novel risk loci (p −8) and report an association in RELN and three previously reported candidate gene or linkage regions (TGFB1, MEPE, and OTSC7). We demonstrate developmental stage-dependent immunostaining patterns of MEPE and RUNX2 in mouse otic capsules. In most association loci, the nearest protein-coding genes are implicated in bone remodelling, mineralization or severe skeletal disorders. We highlight multiple genes involved in transforming growth factor beta signalling for follow-up studies.
Details
- ISSN :
- 20411723
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi...........0b969b55cc1114d06e8444a7f88ec22d