Genetics and Epidemiology of Cholesteatoma in the UK BioBank

Wilson, Emma (2025) Genetics and Epidemiology of Cholesteatoma in the UK BioBank. Doctoral thesis, University of East Anglia.

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Abstract

Cholesteatoma is a skin cyst that grows in the middle ear. It is rare, non-cancerous and locally invasive, frequently resulting in hearing loss due to destruction of the ossicles. Serious and life-threatening sequalae are possible, including facial nerve palsy, meningitis, and abscess of the brain. The only treatment is surgical excision, which can exacerbate hearing loss. There are several theories regarding the origin of cholesteatoma, but its biology is still uncertain. Although not typically considered a heritable disease, observations of family clustering suggest a genetic component. The primary aim of this thesis was to investigate genetic risk of cholesteatoma though genome-wide association study (GWAS) of UK BioBank whole exome data for 1,000 cholesteatoma cases. Single-variant, gene level and gene-set enrichment analyses were performed. This was supported by an epidemiological analysis of demographic factors associated with cholesteatoma and other middle ear disease and a review of global gene expression studies. No single genes or variants met genome-wide significance, but pathways related to cell adhesion, cytoskeletal organisation, ciliary function and calcium binding were enriched for low p-value variants. These results were supported by pathway analysis of summary statistics from a Finnish biobank (FinnGen) and a previous cholesteatoma whole exome study of affected families. Dynein binding was also enriched in UK BioBank whole exome data due to rare DNAH and DNAI family variants, which is promising as DNAH variants were also detected in our previous whole exome study and are known to contribute to similar pathologies such as primary ciliary dyskinesia. These results support the existence of a highly polygenic effect on cholesteatoma risk and indicate several pathways for further study

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User:	Chris White
Date Deposited:	06 Nov 2025 10:00
Last Modified:	06 Nov 2025 10:00
URI:	https://ueaeprints.uea.ac.uk/id/eprint/100912
DOI:

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