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Variants In Wfs1 And Other Mendelian Deafness Genes Are Associated With Cisplatin-Associated Ototoxicity, Heather E. Wheeler, Eric R. Gamazon, Robert Frisina, Carlos Perez-Cervantes, Omar El Charif, Brandon Mapes, Sophie D. Fossa, Darren Feldman, Robert Hamilton, David J. Vaughn, Clair Beard, Chunkit Fung, Chiristian Kollmannsberger, Jeri Kim, Taisei Mushiroda, Michiaki Kubo, Shirin Ardeshir-Rouhani-Fard, Lawrence H. Einhorn, Nancy Cox, M. Eileen Dolan, Lois Travis

Bioinformatics Faculty Publications

Cisplatin is one of the most commonly used chemotherapy drugs worldwide and one of the most ototoxic. We sought to identify genetic variants that modulate cisplatin-associated ototoxicity (CAO). Experimental Design: We performed a genome-wide association study (GWAS) of CAO using quantitative audiometry (4-12 kHz) in 511 testicular cancer survivors of European genetic ancestry. We performed polygenic modeling and functional analyses using a variety of publicly available databases. We used an electronic health record cohort to replicate our top mechanistic finding. Results: One SNP, rs62283056, in the first intron of Mendelian deafness gene WFS1 (wolframin ER transmembrane glycoprotein) and an expression …