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Lookup NU author(s): Dr Jérémie Nsengimana
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2022. Published by Oxford University Press. A number of genomic regions have been associated with melanoma risk through genome-wide association studies; however, the causal variants underlying the majority of these associations remain unknown. Here, we sequenced either the full locus or the functional regions including exons of 19 melanoma-associated loci in 1959 British melanoma cases and 737 controls. Variant filtering followed by Fisher's exact test analyses identified 66 variants associated with melanoma risk. Sequential conditional logistic regression identified the distinct haplotypes on which variants reside, and massively parallel reporter assays provided biological insights into how these variants influence gene function. We performed further analyses to link variants to melanoma risk phenotypes and assessed their association with melanoma-specific survival. Our analyses replicate previously known associations in the melanocortin 1 receptor (MC1R) and tyrosinase (TYR) loci, while identifying novel potentially causal variants at the MTAP/CDKN2A and CASP8 loci. These results improve our understanding of the architecture of melanoma risk and outcome.
Author(s): Castaneda-Garcia C, Iyer V, Nsengimana J, Trower A, Droop A, Brown KM, Choi J, Zhang T, Harland M, Newton-Bishop JA, Bishop DT, Adams DJ, Iles MM, Robles-Espinoza CD
Publication type: Article
Publication status: Published
Journal: Human Molecular Genetics
Year: 2022
Volume: 31
Issue: 17
Pages: 2845-2856
Print publication date: 01/09/2022
Online publication date: 31/03/2022
Acceptance date: 24/03/2022
Date deposited: 20/09/2022
ISSN (print): 0964-6906
ISSN (electronic): 1460-2083
Publisher: Oxford University Press
URL: https://doi.org/10.1093/hmg/ddac074
DOI: 10.1093/hmg/ddac074
PubMed id: 35357426
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