Farré, X.; Blay, N.; Cortés, B.; Carreras, A.; Iraola-Guzmán, S.; de Cid, R. Skin Phototype and Disease: A Comprehensive Genetic Approach to Pigmentary Traits Pleiotropy Using PRS in the GCAT Cohort. Genes2023, 14, 149.
Farré, X.; Blay, N.; Cortés, B.; Carreras, A.; Iraola-Guzmán, S.; de Cid, R. Skin Phototype and Disease: A Comprehensive Genetic Approach to Pigmentary Traits Pleiotropy Using PRS in the GCAT Cohort. Genes 2023, 14, 149.
Farré, X.; Blay, N.; Cortés, B.; Carreras, A.; Iraola-Guzmán, S.; de Cid, R. Skin Phototype and Disease: A Comprehensive Genetic Approach to Pigmentary Traits Pleiotropy Using PRS in the GCAT Cohort. Genes2023, 14, 149.
Farré, X.; Blay, N.; Cortés, B.; Carreras, A.; Iraola-Guzmán, S.; de Cid, R. Skin Phototype and Disease: A Comprehensive Genetic Approach to Pigmentary Traits Pleiotropy Using PRS in the GCAT Cohort. Genes 2023, 14, 149.
Abstract
Human pigmentation has been largely associated with different disease prevalence among populations, but most of these studies are observational and inconclusive. Known to be genetically determined, pigmentary traits have been largely studied by GWAS, mostly in Caucasian ancestry cohorts from North Europe, identifying robustly, several loci involved in many of the pigmentary traits. Here, we conduct a detailed analysis of 13 pigmentary-related traits in a South European cohort of Caucasian ancestry (n=20,000). We observed fair phototype strongly associated with non-melanoma skin cancer and other dermatoses and confirmed by PRS-approach the shared genetic basis with skin and eye diseases, such as melanoma (OR=0.95), non-melanoma skin cancer (OR=0.93), basal cell carcinoma (OR=0.97) and darker phototype with vitiligo (OR=1.02), and cataracts (OR=1.04). Detailed genetic analyses revealed 37 risk loci associated with 10 out of 13 analyzed traits, and 16 fine-mapped genes significantly associated with at least two pigmentary traits. Some of them widely reported, such as MC1R, HERC2, OCA2, TYR, TYRP1, SLC45A2, and unveiling three new candidates RP11-1084J3.4, C1QTNF3 and C17orf112, not reported in GWAS Catalog. These results highlight the importance of phototype assessment as a genetic proxy of skin functionality when evaluating disease screening in mixed populations.
Keywords
Population genetics; Pigmentary traits; Phototype; Pleiotropy; Skin disease; Eye disease
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
,
,
,
,
*
