ArticleEvolution, medicine, and public health2026
Multi-trait analysis of pigmentation traits in relation to skin and ocular cancers: Relevance for evolutionary medicine.
Article in Evolution, medicine, and public health, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background and objectives: Pigmentary traits (skin, hair, eye colour, tanning response) are epidemiologically linked to skin and ocular cancers, but the extent and nature of shared genetic architecture remain incompletely defined. In this study we explored to what extent pigmentation- and cancer-associated variants exhibit pleiotropy. Methodology: We analyzed genome-wide association studies summary statistics from European populations for skin colour; hair colour (blonde, light brown, red, dark brown, black); eye colour; tanning response; and four cancers: cutaneous malignant melanoma (CMM), basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and uveal melanoma (UM). Genetic correlations were estimated with LD score regression. Multi-trait and pairwise pleiotropy were tested with Cross-Phenotype Association. We reviewed available colocalization data (COLOC framework) and post-association functional annotation/mapping (e.g. FUMA) to interpret shared signals. Results: Significant genetic correlations were observed between multiple pigmentary traits and each cancer. Multi-trait and pairwise analyses identified numerous shared regions, including canonical pigmentation loci ( Conclusions and implications: Skin and ocular melanomas illustrate evolutionary mismatch: variants favoured at high latitudes for lighter pigmentation now elevate cancer risk under modern UV exposure. Mapping shared architecture highlights biological pathways that may refine risk prediction, motivate functional studies, and inform prevention strategies. Lay summary: Using genome-wide data, we examined how genes shaping human pigmentation relate to risk of skin and eye melanomas. Multi-trait analyses revealed shared genetics: lighter skin, hair and eye colour, and poor tanning, increased cancer risk. Findings illustrate evolutionary mismatch and highlight pathways that guide prevention, risk prediction, and future research.
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