Original Investigation

Human Genetics

, Volume 132, Issue 2, pp 147-158

Comprehensive candidate gene study highlights UGT1A and BNC2 as new genes determining continuous skin color variation in Europeans

  • Leonie C. JacobsAffiliated withDepartment of Dermatology, Erasmus MC University Medical Center Rotterdam
  • , Andreas WollsteinAffiliated withDepartment of Forensic Molecular Biology, Erasmus MC University Medical Center RotterdamDepartment of Medical Statistics and Bioinformatics, Leiden University Medical Center
  • , Oscar LaoAffiliated withDepartment of Forensic Molecular Biology, Erasmus MC University Medical Center Rotterdam
  • , Albert HofmanAffiliated withDepartment of Epidemiology, Erasmus MC University Medical Center Rotterdam
  • , Caroline C. KlaverAffiliated withDepartment of Epidemiology, Erasmus MC University Medical Center RotterdamDepartment of Ophthalmology, Erasmus MC University Medical Center Rotterdam
  • , André G. UitterlindenAffiliated withDepartment of Epidemiology, Erasmus MC University Medical Center RotterdamDepartment of Internal Medicine, Erasmus MC University Medical Center Rotterdam
  • , Tamar NijstenAffiliated withDepartment of Dermatology, Erasmus MC University Medical Center Rotterdam
  • , Manfred KayserAffiliated withDepartment of Forensic Molecular Biology, Erasmus MC University Medical Center Rotterdam
  • , Fan LiuAffiliated withDepartment of Forensic Molecular Biology, Erasmus MC University Medical Center Rotterdam Email author 

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Abstract

Natural variation in human skin pigmentation is primarily due to genetic causes rooted in recent evolutionary history. Genetic variants associated with human skin pigmentation confer risk of skin cancer and may provide useful information in forensic investigations. Almost all previous gene-mapping studies of human skin pigmentation were based on categorical skin color information known to oversimplify the continuous nature of human skin coloration. We digitally quantified skin color into hue and saturation dimensions for 5,860 Dutch Europeans based on high-resolution skin photographs. We then tested an extensive list of 14,185 single nucleotide polymorphisms in 281 candidate genes potentially involved in human skin pigmentation for association with quantitative skin color phenotypes. Confirmatory association was revealed for several known skin color genes including HERC2, MC1R, IRF4, TYR, OCA2, and ASIP. We identified two new skin color genes: genetic variants in UGT1A were significantly associated with hue and variants in BNC2 were significantly associated with saturation. Overall, digital quantification of human skin color allowed detecting new skin color genes. The variants identified in this study may also contribute to the risk of skin cancer. Our findings are also important for predicting skin color in forensic investigations.