Toggle Main Menu Toggle Search

Open Access padlockePrints

Defining novel causal SNPs and linked phenotypes at melanoma-associated loci

Lookup NU author(s): Dr Jérémie Nsengimana

Downloads


Licence

This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 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.


Publication metadata

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


Altmetrics

Altmetrics provided by Altmetric


Funding

Funder referenceFunder name
076113
825924
A1-S-30165
A3-S-31603
385365
Cancer Research UK
IN209422
NAF\R2\180782
MR/S01473X/1

Share