GWAS meta-analysis provides new insights into uveal melanoma risk
OBJECTIVE: The aim of this research is to identify germline genetic variants that predispose to uveal melanoma (UM) using data from nine studies involving 5839 individuals with UM (3853 novel) and 349,863 healthy controls. METHODS: Five novel UM genome-wide association studies (GWAS) were performed and included for meta-analysis with four previously published UM GWAS. A fixed-effects inverse-variance weighted (IVW) meta-analysis was performed by combining data from these nine UM case-control cohorts. A follow-up transcriptome-wide association study (TWAS) was conducted to identify candidate target genes at UM risk loci. Genetic correlations with melanoma-related phenotypes were measured to elucidate UM's genetic architecture. RESULTS: . TWAS analysis indicates five potential target genes, including MOB3B, RBAK, and MTSS1, which have established links to multiple cancer types. We note a significant genetic correlation (rg = 0.31, P = 0.01) between UM and cutaneous melanoma (CM), and a non-significant but consistent correlation with naevus count (rg = 0.25, P = 0.08). CONCLUSIONS: This meta-analysis offers new insights into the genetic architecture of UM, highlights potential therapeutic targets, and explores the genetic relationship with CM and skin pigmentation.
Authors
- Nathan Ingold (ORCID: https://orcid.org/0000-0002-9668-6275)
- Hauke Thomsen (ORCID: https://orcid.org/0000-0001-5951-3116)
- Asta Försti (ORCID: https://orcid.org/0000-0002-9857-4728)
- David C. Whiteman (ORCID: https://orcid.org/0000-0003-2563-9559)
- Stuart MacGregor (ORCID: https://orcid.org/0000-0001-6731-8142)
- Sarah E. Coupland (ORCID: https://orcid.org/0000-0002-1464-2069)
- Vikas Chadha (ORCID: https://orcid.org/0000-0002-0330-7548)
- Marc‐Henri Stern (ORCID: https://orcid.org/0000-0002-8100-2272)
- Matthew H. Law (ORCID: https://orcid.org/0000-0002-4303-8821)
- Kevin M. Brown (ORCID: https://orcid.org/0000-0002-8558-6711)
- Catherine M. Olsen (ORCID: https://orcid.org/0000-0003-4483-1888)
- Aaron B. Beasley (ORCID: https://orcid.org/0000-0001-5727-7463)
- Julie Connolly (ORCID: https://orcid.org/0000-0002-5542-6100)
- Lenha Mobuchon (ORCID: https://orcid.org/0000-0003-4938-2460)
- Colleen M. Cebulla (ORCID: https://orcid.org/0000-0002-5636-4968)
- Michael Zeschnigk
- Peter A. Johansson (ORCID: https://orcid.org/0000-0001-7015-5452)
- Antonia L. Pritchard (ORCID: https://orcid.org/0000-0001-5336-0454)
- Elin S. Gray (ORCID: https://orcid.org/0000-0002-8613-3570)
- Jane M. Palmer (ORCID: https://orcid.org/0000-0002-2702-522X)
- Helen Kalirai (ORCID: https://orcid.org/0000-0002-4440-2576)
- Ngoc‐Quynh Le (ORCID: https://orcid.org/0000-0002-7797-4925)
- Samantha Barlow (ORCID: https://orcid.org/0000-0003-0163-5043)
- Timothy Beckman (ORCID: https://orcid.org/0000-0002-8364-9643)
- Lindsay A. McGrath (ORCID: https://orcid.org/0000-0003-0925-1124)
- Bechrakis N.E
- Kelly Brooks
- Huanwei Wang (ORCID: https://orcid.org/0000-0002-6137-3391)
- Colette Mustard (ORCID: https://orcid.org/0000-0001-5834-2765)
- Jens F. Kiilgaard (ORCID: https://orcid.org/0000-0003-1054-1460)
- Nick Hayward
- William J. Glasson
- Karin W. Wadt
- Timothy Isaacs
- Lindsey Byrne
- Paul Cauchi
- Gayle Williamson
- Kari Hemminki
- Mohamed H. Abdel-Rahman
- G. J. M. Shanika R. Jayasinghe
- Sunil K. Warrier
- Matthew D’Mellow (ORCID: https://orcid.org/0000-0001-8979-2419)
Institutions
- Edith Cowan University (AU)
- National Institutes of Health (US)
- University of Liverpool (GB)
- Queensland University of Technology (AU)
- The University of Queensland (AU)
- The University of Western Australia (AU)
- German Cancer Research Center (DE)
- Charles University (CZ)
- QIMR Berghofer Medical Research Institute (AU)
- Heidelberg University (DE)
- Université Paris Sciences et Lettres (FR)
- Royal Perth Hospital (AU)
- Harry Perkins Institute of Medical Research (AU)
- Gartnavel General Hospital (GB)
- Rigshospitalet (DK)
- The Ohio State University Wexner Medical Center (US)
- MSB Medical School Berlin (DE)
- Office of the Director (US)
- Hopp Children's Cancer Center Heidelberg (DE)
- Essen University Hospital (DE)
- City Eye Centre (AU)
- National Cancer Institute (US)
- University of the Highlands and Islands (GB)
Publication Details
- Journal
- British Journal of Cancer
- Published
- 2026-06-16
- DOI
- https://doi.org/10.1038/s41416-026-03499-7
- Primary Topic
- Ocular Oncology and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00