All diabetes, all the time

Keeping with the diabetes theme, the first genome-wide association study of Type II diabetes has been published, and it’s extraordinarily promising. Besides picking up the oft-replicated TCF7L2 gene mentioned before, they pick up three other loci, including finding a non-synonymous mutations in a zinc transporter. That’s notable because 1. non-synonymous mutations clearly can have phenotypic effects (there’s no wondering, could this really do something?), and 2. drug targeting of zinc transport is feasible (TCF7L2 is a transcription factor, and when you start playing with transcription factors you risk messing with a lot of pathways). The news article accompanying this study has some good perspective:

In 1918, Ronald Aylmer Fisher, an evolutionary biologist and pioneer of modern statistics, published a paper on the genetic causes of disease that brought together two rival factions. Geneticists promoted a paradigm in which diseases worked a lot like Mendel’s pea plants, with just one or two genes responsible for each condition. Biometricians, however, advocated a continuous distribution of phenotypes. Fisher suggested that many mendelian traits could result in the continuous distribution of a disease. In doing so, he established the conceptual basis for the search for complex disease genes that continues today.

But Fisher’s theories had a more immediate impact on animals and agriculture than on medicine — in people, it’s much easier to study and measure mendelian diseases and traits. Even the much-heralded Human Genome Project in the 1990s didn’t help as much as expected.
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It has taken time for big GWA studies to be completed. “Many people didn’t know how much association studies would deliver,” says Peter Donnelly, a lead investigator of the Wellcome Trust Case Control Consortium, which began collecting samples for GWA studies in 2005.

Yet new results, including a study on type 2 diabetes published this week, suggest that the GWA approach will bear fruit, and lots of it….Modern biology may finally have begun to bring technological and scientific rigour to Fisher’s decades-old insights.