Current opportunities and challenges: genome-wide association studies on pigmentation and skin cancer.

Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
Pigment Cell & Melanoma Research (Impact Factor: 5.84). 07/2012; 25(5):612-7.
Source: PubMed

ABSTRACT Genome-wide association studies (GWAS) have become a widely used approach for genetic association studies of various human traits. A few GWAS have been conducted with the goal of identifying novel loci for pigmentation traits, melanoma, and non-melanoma skin cancer. Nevertheless, the phenotype variation explained by the genetic markers identified so far is limited. In this review, we discuss the GWAS study design and its application in pigmentation and skin cancer research. Furthermore, we summarize recent developments in post-GWAS activities such as meta-analysis, pathway analysis, and risk prediction.

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    ABSTRACT: Mutations within the OCA2 gene or the complete absence of the OCA2 protein leads to Oculocutaneous Albinism type 2. The OCA2 protein plays a central role in melanosome biogenesis, and it is a strong determinant of the eumelanin content in melanocytes. Transcript levels of the OCA2 gene are strongly correlated to pigmentation intensities. Recent studies demonstrated that the transcriptional level of OCA2 is to a large extent determined by the non-coding SNP rs12913832 located 21.5 kb upstream of the OCA2 gene promoter. In this review, we discuss current hypotheses and the available data on the mechanism of OCA2 transcriptional regulation and how this is influenced by genetic variation. Finally, we will explore how future epigenetic studies can be used to advance our insight into the functional biology that connects genetic variation to human pigmentation.
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