Are We Ready to Implement Gwas and Ngs in Diseases Risk Assessment?

Today, Genome Wide Association Studies (GWAS) had been broadly utilized to identify disease risk genes and gene variants, for many disorders in different ethnic backgrounds world-wide. Various uncertainties exist as to how we may interpret the genetic data resulting from such studies, and how to implement genetic information for prognosis or prevention and treatment decisions.

Reasons for uncertainties are for instance due to clinical heterogeneity of diseases, diverse ethnicities underlined by genetic variability, differences in diseases minor alleles’ frequencies across populations, linkage disequilibrium between nearby genetic markers, and the penetrance of the associated genes and their variants.Published gene markers that reached a high enough GWAS significance level need external validation, since they may not necessarily become universal disease markers according to the above reasons.

Hence, the question remains whether these markers are applicable to individuals elsewhere in the same way they are to the population from which they were originally derived. In the search for common grounds in disease genetics, perhaps we at the very minimum need to accept the pathways through which these disease-associated gene markers are dysregulated.These arguments may be illustrated by the complexity associated with the globally prevalent diabetes and obesity, where combinations of genes variations act synergistically, via dysregulated metabolic and endocrinological systems.

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