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Vitiligo pp 237-251 | Cite as

Genetics

  • Richard A. SpritzEmail author
Chapter

Abstract

Large-scale epidemiological surveys have shown that most cases of vitiligo occur sporadically, though about 15–20% of patients report one or more affected relatives. The rationale for genetic studies of vitiligo susceptibility is that underlying genes are involved in mediating disease causation, either increasing or decreasing risk (protective). Three different general approaches have been used to identify genes that mediate vitiligo susceptibility: the candidate gene approach, the genome-wide approach, and the gene expression approach. Extensive experience has proven that the only analytic approach that produces verified discovery of bona fide disease genes is the genome-wide approach. Retrospective analyses of candidate gene studies have shown that the vast majority of claimed candidate gene associations represent false-positives. Accordingly, the candidate gene approach is no longer considered valid for de novo disease gene discovery and is reserved for confirmatory studies only. Similarly, almost all genes that exhibit major expression differences between disease and non-disease states turn out to not correspond to causal genes, but instead represent secondary effects, and thus likewise gene expression studies have generally not led to the discovery of genes that are causal for complex diseases. Indeed, none of the genes initially suggested on the basis of the expression approach now appear to be involved in vitiligo causation at all. In contrast, genome-wide genetic analyses, particularly genome-wide association studies (GWAS), have proven a remarkably robust approach to disease gene discovery, yielding findings that are highly reproducible and which, in aggregate, have provided dramatic advances in understanding the biological basis of many different complex diseases, including vitiligo. Reported candidate gene associations and expression difference findings that are not observed in well-powered GWAS of the same population are not now considered to be valid indications of disease-causal genes and thus will not be discussed here.

Notes

Acknowledgments

This work was supported by grants AR056292 and AR065951 from the National Institutes of Health.

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Authors and Affiliations

  1. 1.Human Medical Genetics and Genomics ProgramUniversity of Colorado School of MedicineAuroraUSA
  2. 2.Department of PediatricsUniversity of Colorado School of MedicineAuroraUSA

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