Novel Insights Into the Etiology of Diabetes From Genome-Wide Association Studies
- From The Population Pharmacogenomics Group, Biomedical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, U.K.
- Corresponding author: Colin N.A. Palmer, nuclear-receptor{at}dundee.ac.uk.
The flood of confirmed genes for type 2 diabetes arising from genome-wide association (GWA) studies has started to raise questions as to the value of such research. Objections stem from the low individual allelic effect sizes (1.1–1.5) and from the recent observations that allele-counting summaries of the current known variants do not add much to the predictive models for type 2 diabetes (1). It has also been suggested that such a large number of variants of this effect size would be required to explain the known heritable component for diabetes that almost every gene could eventually be identified as a type 2 diabetes gene. If this did turn out to be the case, what would be the value of this knowledge (2)? These grumbles come despite the fact that prior to 2007, genetic research in common complex disease had made very little substantive progress either in the realms of candidate gene studies or in the previous generation of genome-wide studies that used microsatellite markers in a linkage paradigm. As noted by Rich, Norris, and Rotter in a commentary last year (3), the results from GWA studies have quickly turned from a trickle to a flood (4–16), and the most immediate advances from this are not disease prediction but, rather, in leading to a better understanding of etiopathogenesis together with identification of novel gene products and pathways as targets for intervention (17).
While the road to drug discovery on such a basis is undoubtedly long and rocky, in terms of disease etiology per se, we are uncovering a wealth of additional knowledge regarding the pathoetiology of type 2 diabetes. First, we are finding that the majority of genetic …
