A large-scale genome-wide association meta-analysis for nevus count provides direct insights into the genetics of melanoma
Jayasinghe, G. J. M. S. R.; Zhu, G.; Pandeya, N.; Olsen, C. M.; Martin, N. G.; Lind, P. A.; Medland, S. E.; Gordon, S. D.; Torres, S. D.; Lingham, G.; Lee, S. S. Y.; Nijsten, T.; Kayser, M.; Pardo, L. M.; Montgomery, G. W.; Hayward, N. K.; Palmer, J. M.; Hunter, D. J.; Han, J.; Hewitt, A. W.; Falchi, M.; Bishop, D. T.; Brown, K. M.; Bataille, V.; Mackey, D. A.; Iles, M. M.; Whiteman, D. C.; Duffy, D. L.; MacGregor, S.; Law, M. H.
Show abstract
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 study (GWAS) included 85,967 individuals of European ancestry. We identified 29 nevus-associated loci (p < 5x10-8), of which 24 were not previously reported in a GWAS conducted for nevus count alone. We further identified 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 prioritised 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. A nevus polygenic risk score explains 5% of the variance in nevus count, indicating its potential to enhance melanoma risk prediction.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.