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Common Disease Common Variant Dead???

Posted Sep 22 2008 4:37pm
I don't think so.....If that is true, I know a few comapnies out West that could have a problem.....

Turns out the publicist formy friend's friendmust have gotten him a sweet article in theNew York Times.

It turns out David Goldstein has been a contrarian forever. It turns out he is getting ready to publish a wonderful book. From the article

"This idea, called the common disease/common variant hypothesis, drove major developments in biology over the last five years. Washington financed the HapMap, a catalog of common genetic variation in the human population. Companies like Affymetrix and Illumina developed powerful gene chips for scanning the human genome. Medical statisticians designed the genomewide association study, a robust methodology for discovering true disease genes and sidestepping the many false positives that have plagued the field."

Well, David argues.....this idea is dead.....

“There is absolutely no question,” he said, “that for the whole hope of personalized medicine, the news has been just about as bleak as it could be.”

Wha????? the common disease common variant theory equal to personalized medicine????

I would say no. What about Pharmacogenomics? I mean, come on...that's what you are studying. What about family history ascertainment? That's what you are publishing. Obviously in your mind, Personalized Medicine is not dead.

But the Common Disease Common Variant issue that is a much more interesting question.

Let's just say it is my Chairman Rick Lifton might also be in agreement with.........What happens? SNP scan testing companies go away.......Affy, Illumina, etc see a drastic cut in their machine usage and purchases (Yikes) and all the hard work we put in for the HapMap gets thrown away.....

No one is going to let that happen. So let's just say it is not dead but on the Injured reserve. If that is the case how do we rehab it.....I have some ideas

1. We need to have better methods of phenotyping and analysis. Common disease is rarely the same in everyone and is likely to have multiple etiologies

2. We need to remember that rare variants interact with common variants and look at this from a systems basis.......I.E. " Both kinds of music Country AND Western" Studies need to be designed this way

3. Lastly, we need to look at the environmental interaction with these common variants. Diet logs, career information, exposures, etc...need to be incorporated into these studies.....

Iff, we do these things and still come up with nothing, then and only then will Common Variant Hypothesis be dead!!! But with the types of ideas on the other side I don't think they get that...From Dr. Goldstein,

Just as selection turns out to have pruned away most disease-causing variants, it has also maximized human cognitive capacities because these are so critical to survival. “My best guess is that human intelligence was always a helpful thing in most places and times and we have all been under strong selection to be as bright as we can be,” he said.

This is more than just a guess, however. As part of a project on schizophrenia, Dr. Goldstein has done a genomewide association study on 2,000 volunteers of all races who were put throughcognitive tests. “We have looked at the effect of common variation on cognition, and there is nothing,” Dr. Goldstein said, meaning that he can find no common genetic variants that affect intelligence. His view is that intelligence was developed early in human evolutionary history and was then standardized.

Seriously? Do you really think Hawkins type of intelligence was the same as Picasso's? What about Mozart's? Einstein's.....The statement that intelligence is standardized is crazy....There is no way a bunch of man made cognitive tests can fully stratify the phenotypes of intelligence......It sounds impressive to the lay reader. But to reeks......

The Sherpa Says: While Dr Goldstein is a smart and learned individual, he will not kill of the Common Variant Hypothesis.
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