Blog brawl, part II
In response to my comments, Juan Carlos Lopez had this reply on Spoonful of Medicine:
Candidate genes? We already have many more candidate genes than we know what to do with. I'd argue that candidate genes are, in fact, part of the "genetic noise" Debra refers to.What this field needs is, among other things, new animal models that allow us to make more thoughtful experiments on the biological basis of psychiatric disease.
In the absence of good models in which to test the functional relevance of whatever genes the screening process identifies, the massive investment that Apoorva highlighted will bring rather paltry returns.
He makes an excellent point, but I'm sticking to my guns. Groups of genes that are subtly affected (not wiped out entirely) would not have been found in the small populations studied thus far. Furthermore, the absence of good animal models underscores the need for more information on variation in the only disease model we have: the human.
Comments
Interesting debate. IMHO Juan Carlos is right on - please, remember that we can model aspects of the pathology associated with psychiatric disorders. Although we will never have a schizophrenic mouse, reproducing and understanding a disease-related parthophysiological process in experimental animals will have an enormous impact on schizophrenia research.
Furthermore, keep in mind that having a predisposing genotype does not yet mean that you will develop the disease. Many of the susceptibility genes will have to interact in a complex manner with various stressors and environmental influences(infections, hypoxia, cannabis use, etc), and this part will be missing from the proposed large-scale genetic studies.
Posted by: Karoly Mirnics | March 26, 2007 05:14 PM
I couldn't agree more, Karoly. Animal models are invaluable to our understanding of psychiatric disorders, and genomics studies on their own won't flesh out mechanisms of pathophysiology. However, I do believe that there is value in these large-scale genomics studies that the field has been slow to appreciate.
I agree that environment cannot be ignored as a factor contributing to disease, and certainly there are many better techniques to address environmental impact. But as Sebat et al. (currently online ahead of print) report in Science, large-scale genomics studies don't necessarily ignore environmental factors. These authors report that children with autism show copy number variations absent in their parents, suggesting that environmental factors may cause genetic mutations that contribute to autism.
Posted by: Debra Speert | March 27, 2007 11:05 AM
Maybe JCL thinks "candidate genes" means ORFs? I suppose the new money is for SNPs, which generates a more faithful breed of candidate genes. JCL seems to be saying disease genetics has relatively little to tell us about psychosis. He wants to bet all the money on nurture and none on nature.
Posted by: MT | April 20, 2007 04:02 PM