Work

Population- and haplotype-dependent variation around TYR rs1126809: An in silico study for melanoma risk research

Year: 2025

Type: article

Abstract: The common missense variant rs1126809 in the TYR gene, encoding a key enzyme in melanin synthesis, is linked to both albinism and melanoma susceptibility. Although its role in hypopigmentation as part of a risk haplotype is established, its function in melanoma is less understood. To investigate population- and haplotype-dependent associations surrounding TYR rs1126809 that may suggest directions for future studies on melanoma risk and melanocyte biology, we analyzed melanoma GWAS summary statistics using FUMA to identify lead SNPs in linkage disequilibrium with rs1126809 and assessed their regulatory potential using chromatin state data from melanocytes, keratinocytes, and fibroblasts. Haplotype structures were examined in European, American, and South Asian populations using LDlink. rs1126809 emerged as lead SNP in the TYR locus. Thirty SNPs were in high linkage disequilibrium, 6 of which reside in melanocyte-specific regulatory regions. These variants form population-specific haplotypes that may modulate TYR expression. In Europeans and Americans, 2 distinct haplotypes carrying the risk allele showed different linked SNP profiles, suggesting haplotype-dependent effects. The findings suggest that variations surrounding TYR rs1126809 may exhibit population- and haplotype-dependent patterns relevant to melanoma risk, pointing to previously unreported directions for future research and refinement of polygenic risk modeling.

Source: JID Innovations

DOI: 10.1016/j.xjidi.2025.100445

Authors: Árpád Ármin Balogh, Márta Széll, Nikoletta Nagy

Institution: University of Szeged

Language: English

Topic: melanin and skin pigmentation

Subfield: Cell Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,000