[girija]

Here is an article worth reading to balance the euphoria of DNA testing and possible cures. Enjoy!
Girija


Article Tools Sponsored By
By NICHOLAS WADE
Published: April 15, 2009

The era of personal genomic medicine may have to wait. The genetic analysis of common disease is turning out to be a lot more complex than expected
David B. Goldstein of Duke University is among the geneticists who are debating which path to follow in disease research.

Since the human genome was decoded in 2003, researchers have been developing a powerful method for comparing the genomes of patients and healthy people, with the hope of pinpointing the DNA changes responsible for common diseases.

This method, called a genomewide association study, has proved technically successful despite many skeptics’ initial doubts. But it has been disappointing in that the kind of genetic variation it detects has turned out to explain surprisingly little of the genetic links to most diseases.

A set of commentaries in this week’s issue of The New England Journal of Medicine appears to be the first public attempt by scientists to make sense of this puzzling result.

One issue of debate among researchers is whether, despite the prospect of diminishing returns, to continue with the genomewide studies, which cost many millions of dollars apiece, or switch to a new approach like decoding the entire genomes of individual patients.

The unexpected impasse also affects companies that offer personal genomic information and that had assumed they could inform customers of their genetic risk for common diseases, based on researchers’ discoveries.

These companies are probably not performing any useful service at present, said David B. Goldstein, a Duke University geneticist who wrote one of the commentaries appearing in the journal.

“With only a few exceptions, what the genomics companies are doing right now is recreational genomics,” Dr. Goldstein said in an interview. “The information has little or in many cases no clinical relevance.”

Unlike the rare diseases caused by a change affecting only one gene, common diseases like cancer and diabetes are caused by a set of several genetic variations in each person. Since these common diseases generally strike later in life, after people have had children, the theory has been that natural selection is powerless to weed them out.

The problem addressed in the commentaries is that these diseases were expected to be promoted by genetic variations that are common in the population. More than 100 genomewide association studies, often involving thousands of patients in several countries, have now been completed for many diseases, and some common variants have been found. But in almost all cases they carry only a modest risk for the disease. Most of the genetic link to disease remains unexplained.

Dr. Goldstein argues that the genetic burden of common diseases must be mostly carried by large numbers of rare variants. In this theory, schizophrenia, say, would be caused by combinations of 1,000 rare genetic variants, not of 10 common genetic variants.

This would be bleak news for those who argue that the common variants detected so far, even if they explain only a small percentage of the risk, will nonetheless identify the biological pathways through which a disease emerges, and hence point to drugs that may correct the errant pathways. If hundreds of rare variants are involved in a disease, they may implicate too much of the body’s biochemistry to be useful.

“In pointing at everything,” Dr. Goldstein writes in the journal, “genetics would point at nothing.”

Two other geneticists, Peter Kraft and David J. Hunter of the Harvard School of Public Health, also writing in the journal, largely agree with Dr. Goldstein in concluding that probably many genetic variants, rather than few, “are responsible for the majority of the inherited risk of each common disease.”

But they disagree with his belief that there will be diminishing returns from more genomewide association studies.

“There will be more common variants to find,” Dr. Hunter said. “It would be unfortunate if we gave up now.”

Dr. Goldstein, however, said it was “beyond the grasp of the genomewide association studies” to find rare variants with small effects, even by recruiting enormous numbers of patients. He said resources should be switched away from these highly expensive studies, which in his view have now done their job.

“If you ask what is the fastest way for us to make progress in genetics that is clinically helpful,” he said, “I am absolutely certain it is to marshal our resources to interrogate full genomes, not in fine-tuning our analyses of common variations.”

He advocates decoding the full DNA of carefully selected patients.

Dr. Kraft and Dr. Hunter say that a person’s genetic risk of common diseases can be estimated only roughly at present but that estimates will improve as more variants are found. But that means any risk estimate offered by personal genomics companies today is unstable, Dr. Kraft said, and subject to upward or downward revision in the future.

Further, people who obtain a genomic risk profile are likely to focus with horror on the disease for which they are told they are at highest risk. Yet this is almost certain to be an overestimate, Dr. Kraft said.

The reason is that the many risk estimates derived from a person’s genomic data will include some that are too high and some that are too low. So any estimate of high risk is likely to be too high. The phenomenon is called the “winner’s curse,” by analogy to auctions in which the true value of an item is probably the average of all bids; the winner by definition has bid higher than that, and so has overpaid.

Dr. Kari Stefansson, chief executive of deCODE Genetics, an Icelandic gene-hunting company that also offers a personal genome testing service, said deCODE alerted clients to pay attention to diseases for which testing shows their risk is three times as great as average, not to trivial increases in risk.

Dr. Stefansson said his company had discovered 60 percent of the disease variants known so far.

“We have beaten them in every aspect of the game,” he said of rival gene hunters at American and British universities.

The undiscovered share of genetic risk for common diseases, he said, probably lies not with rare variants, as suggested by Dr. Goldstein, but in unexpected biological mechanisms. DeCODE has found, for instance, that the same genetic variant carries risks that differ depending on whether it is inherited from the mother or the father

[SherylJ]

What does this article say about the potential value of the data to be generated by the Google/Fox/23 and Me Project? I do not understand the science well enough to draw my own conclusion. I want to trust that those in charge are focused on quality of data as well as quantity so further research rests on a strong foundation.
sheryl

[reverett123]

...it appears to me that the view of our genes as making up a marvelous blueprint is wrong and that it is more that they make up a great reference work. Most entries are never read.

[indigogo]

I have approached the 23andMe project as being a way to build a potentially beneficial database for research, not as a way to predict my propensity for certain diseases. As far as I can tell, gene research is not going to end - they are just learning more as they go along, as is always the case.

[paula_w]

This article came in pipeline email this morning and I've been thinking about it off and on. The factors that i am considering are listed. feel free to add to it - with the right answer an unknown:

I wouldn't be surprised if we never figure it out.

The doctor in this article has a competing business.

He could be right.

He is referring to what seems like exactly the kind if study being conducted by 23andme.

I refer to posts such as hiptothat and tutor50 in the 23andme thread. Who knows what else might turn up?

we've got nothing to lose.

If the medical communities are not going to be accepting of it [no surprise], then the insurance companies can't use it against anyone.

We'll never know anything if we don't try it.

It's just spit. I don't see it as a big deal because it's so cheap.

23andme isn't hiding anything.

i agree that they did appear to be more of a social [recreational i believe he said]gnenomic company. they also do not claim to have done serious illness studies prior to this. we are the first.

they are only testing for two known gene variants.

i have a hard time fathoming that nothing would turn up - nothing at all- if ten thousand people donated spit and....this and is imperative to include...fill out surveys to collect info in a huge database.

it is demeaning for the doctor to assume that people can't understand the risks and averages he spoke of but instead would react with horror to the possibilities. if that is the state of mind one is in , he/she should not get the analysis.

i think people with pd are more savvy than he may think they are.

there are no guarantees. we all know that.

i don't believe what i read by the medical community anymore [sadly], particularly when they own a business or a patent, or are editors of journals. i know there are many good - honest people in the medical community. but how many doctors does one person encounter in a lifetime? not nearly enough to know who is honest and who isn't.

question for rick....what do you mean when you say: they aren't read? i just didn't follow you there...can you explain? thanks.

already thought of two more things:

i wouldn't make this decision or change my mind from yes to no based on this article alone. that isn't suggesting that you shouldn't - i'm saying i wouldn't.

Sergey Brins' mother isn't just the mother with pd. She was a scientist at NASA and is on the new MJFF patient advisory committee.

[KC Tower]

Originally Posted by paula_w

I don't see it as a big deal because it's so cheap.

23andme isn't hiding anything.

Again, $25 wouldn't cause me to bat an eye but the feeling of being misled and finding that it is $85USD for those of us in Canada makes me sit this out ....

unless someone convinces me that it would have been worth $85 to them for their own test or for me to spend for my test to benefit all.

If they want it US only just say so.....

take care ,,,, ken

[paula_w]

i wouldn't pay $85 either ken. Other things that cost $85 have a higher priority in my budget. There are other billionaires with pd out there i'm sure. I think 23andme should consider getting another grant to make this globally cheap. It's important to have as many ethnic and geographic areas as possible included. i won't try to convince you. i think someone should convince or fund them. It likely will have an effect on the validity of info.

This is a different population than one who can afford recreational gnenomics. Perhaps this will be considered..it must be hard to look at $85 as expensive when you are a billionaire. ...but they want to do this and have reduced it quickly so i think it's worth mentioning [Debi? what do you think?] Has this come up ?- i don't mean you funding them..you have to stay focused on finding treatments and a cure without a placebo effect messing it up....lol [not kidding tho], but wondered if you had any info to share about this.


paula

Originally Posted by KC Tower

Again, $25 wouldn't cause me to bat an eye but the feeling of being misled and finding that it is $85USD for those of us in Canada makes me sit this out ....

unless someone convinces me that it would have been worth $85 to them for their own test or for me to spend for my test to benefit all.

If they want it US only just say so.....

take care ,,,, ken

[reverett123]

Paula-

First, genetics is a weak area for me, so if I mess this up please understand...

What I was referring to was that there seems to be a large part of the genome that does nothing unless it is activated by the environment. The term "epigenetics" is applied, I believe. But the thing is that genes are turned on and off as needed, sometimes several times a day. It is not a static blueprint being slavishly copied but is actually a dynamic beehive of activity.

Originally Posted by paula_w

This article came in pipeline email this morning and I've been thinking about it off and on. The factors that i am considering are listed. feel free to add to it - with the right answer an unknown:

I wouldn't be surprised if we never figure it out.

The doctor in this article has a competing business.

He could be right.

He is referring to what seems like exactly the kind if study being conducted by 23andme.

I refer to posts such as hiptothat and tutor50 in the 23andme thread. Who knows what else might turn up?

we've got nothing to lose.

If the medical communities are not going to be accepting of it [no surprise], then the insurance companies can't use it against anyone.

We'll never know anything if we don't try it.

It's just spit. I don't see it as a big deal because it's so cheap.

23andme isn't hiding anything.

i agree that they did appear to be more of a social [recreational i believe he said]gnenomic company. they also do not claim to have done serious illness studies prior to this. we are the first.

they are only testing for two known gene variants.

i have a hard time fathoming that nothing would turn up - nothing at all- if ten thousand people donated spit and....this and is imperative to include...fill out surveys to collect info in a huge database.

it is demeaning for the doctor to assume that people can't understand the risks and averages he spoke of but instead would react with horror to the possibilities. if that is the state of mind one is in , he/she should not get the analysis.

i think people with pd are more savvy than he may think they are.

there are no guarantees. we all know that.

i don't believe what i read by the medical community anymore [sadly], particularly when they own a business or a patent, or are editors of journals. i know there are many good - honest people in the medical community. but how many doctors does one person encounter in a lifetime? not nearly enough to know who is honest and who isn't.

question for rick....what do you mean when you say: they aren't read? i just didn't follow you there...can you explain? thanks.

already thought of two more things:

i wouldn't make this decision or change my mind from yes to no based on this article alone. that isn't suggesting that you shouldn't - i'm saying i wouldn't.

Sergey Brins' mother isn't just the mother with pd. She was a scientist at NASA and is on the new MJFF patient advisory committee.

[bluedahlia]

Originally Posted by KC Tower

Again, $25 wouldn't cause me to bat an eye but the feeling of being misled and finding that it is $85USD for those of us in Canada makes me sit this out ....

unless someone convinces me that it would have been worth $85 to them for their own test or for me to spend for my test to benefit all.

If they want it US only just say so.....

take care ,,,, ken

$85 US equates $102 CDN. That's where my order ended. I'm on a fixed income...can't afford it.

[paula_w]

thank BDahlia for letting me know. we are expecting their portion of the video any time now, in fact Carol may have received it today. If , by chance that has been addressed on it i will of course let you know. otherwise, i will ask lizzie, the point person. it seems that 10,000 would be much easier to reach if the entire online world were included. or debi brooks, if you see this and have any comment would appreciate it.

rick, i wouldn't have a clue if you messed up but it makes sense. our bodies are so awesome, like i have said, learning about them is so interesting it's a coping mechanism in itself. would it be correct to say we are now dealing with bits of information instead of cells? what do i know? nothing - wide open for another parkinson's degree in genetics. lol bring it on.....i can't help but almost chuckle at the presumption that we can crack this code but i can hope for symptom relief. we need to clean up the earth and live simply....fat chance. i'm doing it, because simply is all i can handle....it's easier too.

paula