Castaneda-Garcia, C, Iyer, V, Nsengimana, J et al. (11 more authors) (2022) Defining novel causal SNPs and linked phenotypes at melanoma-associated loci. Human Molecular Genetics, 31 (17). pp. 2845-2856. ISSN 0964-6906
Abstract
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.
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Copyright, Publisher and Additional Information: | © The Author(s) 2022. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. | ||||||
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Institution: | The University of Leeds | ||||||
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Depositing User: | Symplectic Publications | ||||||
Date Deposited: | 16 Jun 2022 15:54 | ||||||
Last Modified: | 29 Oct 2022 12:36 | ||||||
Status: | Published online | ||||||
Publisher: | Oxford University Press | ||||||
Identification Number: | https://doi.org/10.1093/hmg/ddac074 | ||||||
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