Tuesday, July 03, 2007

Diabetes: Deja vu all over again

This week's Nature Genetics advance publication abstracts (you need a subscription to access the full text; I don't have one) brought more genetic association studies. These studies are coming in at a furiohttp://www.blogger.com/post-create.g?blogID=36768584
Blogger: Omics! Omics! - Create Postus pace, with the rate expected only to increase.

A huge issue with association studies is whether they are correct. The field has been tainted by early studies that failed to hold up to later scrutiny. The sheer frequency of new genetic associations makes watching the field challenging, and I don't claim to keep up in general. Many of these studies turn up variants in genes which have been little if at all characterized, and the biological follow-up is often slow -- because it is slow, hard work.

What struck me about these two papers was first that they were both about common variants & diabetes. What is even more interesting is that in each case the study found common variants affecting diabetes risk that were in genes already strongly associated with diabetes.

A group including deCODE Genomics identified variants in TCF2 (aka HNF1-beta), a gene already associated with Mature Onset Diabetes of the Young, or MODY. When I first came to Millennium there was a race on to find one of the MODY genes, which resulted in finding HNF1-alpha (albeit after the other group). Other members of the HNF family cause MODY when mutated.

The other group found protective mutations in the WFS1 gene, which when mutated causes Wolfram syndrome. Strikingly, among the major symptoms of Wolfram syndrome are diabetes, though with a bunch of nasty developmental defects thrown in. Now, it wasn't entirely surprising that this study nailed a known gene in diabetes, because they focused on genes with known relevance to pancreatic beta cell biology. But it still beats gene of unknown function #10,001.

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