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| PMID |
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| TITLE |
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| A large-scale genome-wide association meta-analysis for nevus count provides direct insights into the genetics of melanoma. |
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| ABSTRACT |
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| A greater understanding of the biology of nevi will provide insights into the etiology of melanoma. Our large-scale meta-analysis of 14 nevus genome-wide association studies (GWAS) includes 85,965 individuals of European ancestry. We identify 29 nevus-associated loci (p < 5 × 10 ), of which 24 have not been previously reported in a GWAS conducted for nevus count alone. We further identify 255 candidate genes for nevus loci, including SIKE1 which is involved in immune response regulation. This is of interest because immune response regulation influences the formation of nevi and melanoma susceptibility. Gene-set enrichment analyses prioritise immune response-related pathways and cancers that do not have a pigmentation component (e.g. breast, prostate, and glioma). This suggests that the biology underlying nevus count captures risk pathways beyond pigmentation that are relevant to melanoma. In sex-specific analyses, we observe higher total-body nevus count in females than in males, however the genetic architecture is largely shared (genetic correlation = 0.863, 95% CI = 0.453 - 1.273), indicating the difference may be influenced by environmental and behavioural factors rather than genetics. A nevus polygenic risk score explains 5% of the variance in nevus count, indicating its potential to enhance melanoma risk prediction. |
| © 2026. The Author(s). |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| received |
2025/02/20 |
| accepted |
2026/02/25 |
| medline |
2026/04/24 00:32 |
| pubmed |
2026/03/11 06:58 |
| entrez |
2026/03/11 00:18 |
| pmc-release |
2026/03/10 |
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| AUTHORS |
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| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Jayasinghe GJMSR |
|
Jayasinghe |
G J M Shanika R |
GJMSR |
|
School of Biomedical Sciences, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland, Brisbane, QLD, Australia. shanika.jayasinghe@qimrb.edu.au. |
| Zhu G |
|
Zhu |
Gu |
G |
|
Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. |
| Pandeya N |
|
Pandeya |
Nirmala |
N |
|
School of Public Health, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland, Brisbane, QLD, Australia. |
| Olsen CM |
|
Olsen |
Catherine M |
CM |
|
Dermatology Research Centre, Frazer Institute, The University of Queensland, Brisbane, QLD, Australia. |
| Martin NG |
|
Martin |
Nicholas G |
NG |
|
Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. |
| Lind PA |
|
Lind |
Penelope A |
PA |
|
School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia. |
| Medland SE |
|
Medland |
Sarah E |
SE |
|
School of Psychology, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland, Brisbane, QLD, Australia. |
| Gordon SD |
|
Gordon |
Scott D |
SD |
|
Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. |
| Diaz-Torres S |
|
Diaz-Torres |
Santiago |
S |
|
Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. |
| Lingham G |
|
Lingham |
Gareth |
G |
|
Centre for Eye Research Australia, East Melbourne, VIC, Australia. |
| Lee SSY |
|
Lee |
Samantha S Y |
SSY |
|
Centre for Ophthalmology and Visual Science (incorporating the Lions Eye Institute), The University of Western Australia, Nedlands, WA, Australia. |
| Nijsten T |
|
Nijsten |
Tamar |
T |
|
Department of Dermatology, Erasmus MC Cancer Institute, Erasmus MC University Medical Centre Rotterdam, Rotterdam, The Netherlands. |
| Kayser M |
|
Kayser |
Manfred |
M |
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Department of Pathology and Clinical Bioinformatics, Erasmus MC Cancer Institute, Erasmus MC University Medical Centre Rotterdam, Rotterdam, The Netherlands. |
| Pardo LM |
|
Pardo |
Luba M |
LM |
|
Department of Dermatology, Erasmus MC Cancer Institute, Erasmus MC University Medical Centre Rotterdam, Rotterdam, The Netherlands. |
| Montgomery GW |
|
Montgomery |
Grant W |
GW |
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Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia. |
| Hayward NK |
|
Hayward |
Nicholas K |
NK |
|
Oncogenomics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. |
| Palmer JM |
|
Palmer |
Jane M |
JM |
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Oncogenomics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. |
| Hunter DJ |
|
Hunter |
David J |
DJ |
|
Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. |
| Han J |
|
Han |
Jiali |
J |
|
Melvin and Bren Simon Comprehensive Cancer Center, Indiana University, 1050 Wishard Boulevard, Indianapolis, IN, USA. |
| Hewitt AW |
|
Hewitt |
Alex W |
AW |
|
Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia. |
| Falchi M |
|
Falchi |
Mario |
M |
|
Department of Twin Research and Genetic Epidemiology, King's College London, London, UK. |
| Bishop DT |
|
Bishop |
D Timothy |
DT |
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Leeds Institute for Data Analytics, University of Leeds, Leeds, UK. |
| Brown KM |
|
Brown |
Kevin M |
KM |
|
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. |
| Bataille V |
|
Bataille |
Veronique |
V |
|
Department of Dermatology, Hemel Hempstead Hospital, West Hertfordshire NHS Trust, Hemel Hempstead, UK. |
| Mackey DA |
|
Mackey |
David A |
DA |
|
Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia. |
| Iles MM |
|
Iles |
Mark M |
MM |
|
NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK. |
| Whiteman DC |
|
Whiteman |
David C |
DC |
|
Cancer Control Group, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. |
| Duffy DL |
|
Duffy |
David L |
DL |
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Dermatology Research Centre, Frazer Institute, The University of Queensland, Brisbane, QLD, Australia. |
| MacGregor S |
|
MacGregor |
Stuart |
S |
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Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. |
| Law MH |
|
Law |
Matthew H |
MH |
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School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia. Matthew.Law@qimrb.edu.au. |
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| INVESTIGATORS |
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| JOURNAL |
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| VOLUME: 17 |
| ISSUE: 1 |
| TITLE: Nature communications |
| ISOABBREVIATION: Nat Commun |
| YEAR: 2026 |
| MONTH: Mar |
| DAY: 10 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 2041-1723 |
| ISSNTYPE: Electronic |
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| MEDLINE JOURNAL |
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| MEDLINETA: Nat Commun |
| COUNTRY: England |
| ISSNLINKING: 2041-1723 |
| NLMUNIQUEID: 101528555 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
| Meta-Analysis |
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| COMMENTS AND CORRECTIONS |
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| REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
| UpdateOf |
medRxiv. 2025 Feb 25:2025.02.25.25322831. doi: 10.1101/2025.02.25.25322831. |
41030926 |
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| GRANTS |
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| GENERAL NOTE |
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| KEYWORDS |
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| MESH HEADINGS |
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| DESCRIPTORNAME |
QUALIFIERNAME |
| Humans |
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| Genome-Wide Association Study |
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| Melanoma |
pathology |
| Male |
pathology |
| Female |
pathology |
| Genetic Predisposition to Disease |
pathology |
| Nevus |
pathology |
| Skin Neoplasms |
pathology |
| Polymorphism, Single Nucleotide |
pathology |
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| SUPPLEMENTARY MESH |
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| GENE SYMBOLS |
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| CHEMICALS |
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| OTHER ID's |
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