Human Genetics

, Volume 132, Issue 2, pp 147–158 | Cite as

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

  • Leonie C. Jacobs
  • Andreas Wollstein
  • Oscar Lao
  • Albert Hofman
  • Caroline C. Klaver
  • André G. Uitterlinden
  • Tamar Nijsten
  • Manfred Kayser
  • Fan LiuEmail author
Original Investigation


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.


Skin Color Color Dimension Skin Darkness Sulem Oculocutaneous Albinism 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors are grateful to the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists. We also thank Paulus de Jong and Astrid Fletcher for their contribution in establishing the eye picture collection. We thank Pascal Arp, Mila Jhamai, Marijn Verkerk, Lizbeth Herrera and Marjolein Peters for their help in creating the GWAS database, and Karol Estrada and Maksim V. Struchalin for their support in creation and analysis of imputed data.

The generation and management of GWAS genotype data for the Rotterdam Study are supported by the Netherlands Organisation of Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012). This study is funded by the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) project nr. 050-060-810. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), the Municipality of Rotterdam and the Netherlands Forensic Institute (NFI) within the frameworks of the Forensic Genomics Consortium Netherlands (FGCN) and the Netherlands Consortium on Healthy Ageing (NCHA).

Conflict of interest

The authors declare no conflicts of interest.

Supplementary material

439_2012_1232_MOESM1_ESM.doc (596 kb)
Supplementary table 1 (DOC 599 kb)
439_2012_1232_MOESM2_ESM.doc (173 kb)
Supplementary table 2 (DOC 173 kb)
439_2012_1232_MOESM3_ESM.doc (70 kb)
Supplementary table 3 (DOC 69 kb)
439_2012_1232_MOESM4_ESM.doc (66 kb)
Supplementary table 4 (DOC 65 kb)
439_2012_1232_MOESM5_ESM.tif (1.3 mb)
Supplementary Figure 1a. Example photographs used in this study before masking the eye area. (TIFF 1305 kb)
439_2012_1232_MOESM6_ESM.tif (1.2 mb)
Supplementary Figure 1b. Example photographs used in this study after masking the eye area. (TIFF 1231 kb)
439_2012_1232_MOESM7_ESM.tif (8.3 mb)
Supplementary Figure 2a. Hue-Brightness color space of the study subjects (N=5,860). The colors represent perceived skin darkness, classified into very white (purple dots), white (yellow dots), and white to olive (blue dots). (TIFF 8500 kb)
439_2012_1232_MOESM8_ESM.tif (2.4 mb)
Supplementary Figure 2b. Brightness-Saturation color space of the study subjects (N=5,860). The colors represent perceived skin darkness, classified into very white (purple dots), white (yellow dots), and white to olive (blue dots). (TIFF 2432 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Leonie C. Jacobs
    • 1
  • Andreas Wollstein
    • 2
    • 3
  • Oscar Lao
    • 2
  • Albert Hofman
    • 4
  • Caroline C. Klaver
    • 4
    • 5
  • André G. Uitterlinden
    • 4
    • 6
  • Tamar Nijsten
    • 1
  • Manfred Kayser
    • 2
  • Fan Liu
    • 2
    Email author
  1. 1.Department of DermatologyErasmus MC University Medical Center RotterdamRotterdamThe Netherlands
  2. 2.Department of Forensic Molecular BiologyErasmus MC University Medical Center RotterdamRotterdamThe Netherlands
  3. 3.Department of Medical Statistics and BioinformaticsLeiden University Medical CenterLeidenThe Netherlands
  4. 4.Department of EpidemiologyErasmus MC University Medical Center RotterdamRotterdamThe Netherlands
  5. 5.Department of OphthalmologyErasmus MC University Medical Center RotterdamRotterdamThe Netherlands
  6. 6.Department of Internal MedicineErasmus MC University Medical Center RotterdamRotterdamThe Netherlands

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