NIH Draft Consensus Statement on Family History

The NIH conference on Family History came and went.

What were we left with?

A Consensus Statement.

What is the crux of it?

"The panel recognized that family history has an important role in the practice of medicine and may motivate positive lifestyle changes, enhance individual empowerment, and influence clinical interventions. The panel found that it is unclear how this information can be effectively gathered and used in the primary care setting for common diseases."


Well ladies and gentlemen. I can give you all sorts of anecdotal evidence. That being said, we are evidence driven creatures, so I suggest you give me a call and we set up studies in Primary Care practices with different family history tools.

Things such as the "SCREEN" screen versus a detailed 3 generation pedigree versus 1st generation.

It is pretty easy and inexpensive to set these studies up if you use current technologies.

What else did the panel say?

"For a systematically collected family history for common diseases to become an evidence-based tool in primary care clinical settings, substantial additional research will be needed."

I agree, it is time we develop these tools as multifactorial shotguns which hit lots of targets. This IS what DTC is arguing that there puny little scans do. Without evidence Family History champions like myself run the risk of sounding like the marketing hacks out in Silicon Valley and PR firms like NYC.

That being said there are some evidence tools where Family History helps clinical classification. I think specifically of the Reynolds Risk and how it beat the Framingham

We should attack this one precisely the same way. Start by each individual risk calculator ADD family history and see what it does.

Then do a cohort study of practices which routinely perform 3 generation pedigrees and see how the incidence of diseases like diabetes, HTN and MI shake out.

That could be done over 5-10 years. Not a long wait to get some great evidence, if you ask me.

The Sherpa Says: The evidence may be weak for Family History as a Poly-Tool. But as a clinical marker in certain diseases it is ESSENTIAL.

Where from here?

This is the question I am asked so often.

1. We have the steady progress towards cheap genomes.
2. We have the biggest supporter of personalized medicine running the NIH
3. We have "some" clinical awareness of personalized medicine
4. We have the government aware of the shenanigans of some unscrupulous DTC advertising, etc
5. We have several milemarkers under our belts with genome science..... We are moving in the "right" direction, but where do we go from here

There are several areas we need to investigate. I would like to sum a few of them, both basic science and clinical. Basic Science first.

1. We need to understand precisely how gene regulation occurs in the face of certain common environmental exposures. Trans Fat, Tobacco Smoke, Alcohol, Stress. Is it RNA? Is it Methylation? What precisely is it? Maybe it is all of them and more. But the quicker we understand that, the quicker we can look for signs of these ill effects.....and stop them molecularly

2. We need a good CNV/Indel etc database. Toronto sure, I have heard that. But seriously. We need this and we need it now. Give me Normals, Give me abnormals, Give me phenotypes......This is a very key missing piece of the puzzle which neds to be completed in the next 2 years

3. Junk DNA investigation. This will come once we have a database like the one in Iceland......I am certain this will come. I think that next to nuclear fission, the investigation into the "junk dna" will prove to be one of the most fruitful works of governmental science. Yes, you can quote me on that one.

4. Systems biology. This is one of those areas where we will eventually realize the Greeks were right with phlegmatic systems vs bilious systems.......

Now onto the top 3 Clinical Science targets

1. A complete revamping of the current risk stratification system. What do I mean? We need to develop a process for efficiently introducing genotypic risks into current clinical risk stratification. We need to evaluate the with and without and change in AUC......
1b. We need to evaluate the role of integrating family history in some risk stratification models. I know Dr. Khoury/Scheuner et.al are working on these things, but it sure would be nice to have odds ratios and RRs/HRs for adverse drug outcomes, common autoimmune disease risks, COPD, Alcoholism, Suicide, etc. types based on fam hx integrated with current models.

2. Pharmacogenomics......end of story, we need more science here for more drugs. There is not nearly enough clinical study weight on outcomes. I understand why from the Pharma end, but the US government cannot ignore its utility, especially with the pain they feel from Medicare part D
This area has tremendous promise, but has not seen the will from genetics departments, mine looked at my cross eyed when I wanted to do a PGx study. There has to be a will in basic medical science departments like pharmacology and cell biology to understand the processes and polymorphism which really screw up a drug's effect.....or really enhance it. And there has to be a will in clinical departments to study the outcomes with different therapies based on genes.....

3. I want to know what behavioral outcomes are likely with knowledge of one's family history risk versus genome scan risk vs both together vs with no knowledge.

These are some low hanging fruit that could get accomplished and probably already are........

The Sherpa Says: These are not stretch targets, these are do-able things in the next 5 years or so. If we can accomplish most of these, we will be well on our way to evidence based personalized medicine, which is where we need to be........

Family History, State of the Science

The NIH/CDC is hosting a conference next week. I conference I wish I could go to, but alas, I will be DOING family histories on my patients that week.

The conference will be held at the NIH in Bethesda. This is an NIH state of the science conference about Family History and its usefulness.

I for one, am very glad that the government is trying to address this super important issue. It is beyond due for an evaluation.

Why?

With the cost of a genome going to drop to 5000 USD by the late fall (trust me), we will soon see another level of DTC and Clinical lab set offering the genome as a predictive tool.

There are several reasons that Family History beats a Genome (For Now)
1. Phenotypic data of family history represents complex interplay of genes and environment

There is no way that a simple genome will be able to give us the story of how a human will develop. That is predicted by environment and genes, which are successfully covered by..... A family history.

2. 5000 USD is still more than what it costs to obtain a family history.

By the time the software tools are released, we will see that social networking and the internet will transform the costs of family history next to nothing. Which is still a long way to go for the genome scans.

3. We have no clue what most of the genome data means.

Indels or CNVs or SNPs, we have no freaking clue what most mean, we do know what a heart attack at 40 means.......

4. Even if we had everyone's genome scans, we would still need phenotypic data and pedigrees.

What's the one thing we do when we have an intellectually delayed child with an abnormal CMA/CGH? We test the parents. Looking for THEIR phenotypes to make sense of the genome mess.

Look, people always give me reasons why the genome is important and a family history is useless.
I've heard them.

-"We don't speak with that side of the family"
-"My father lived with his uncle, because his father died (secretly running the empire as Darth Vader)"
-"I was adopted by Bail Organa, only to find out I have a lost twin brother"

There is one thing that will always be certain over time, there will be some screwed up family dynamics making it difficult (BUT NOT IMPOSSIBLE) to obtain an accurate family history.

That being said, it is still often useful to capture those who you can. And still less expensive.

I look forward to the briefings from this conference, and Muin, if you are listening, I would love to have the link to the webcasts.... Oh wait, they have that too! Sweet.

If you can't be there, you can get the information you seek!

Once again, we need a state of the science on genome prediction, not a consensus statement a real eval of the state of the science. When placed side by side with the state of the science for a family history, we will soon see why family history is the preferred screening tool and will likely to continue that way, perhaps in conjunction with a genome scan, but genomes will NEVER replace family history.

The Sherpa Says: The press better be at this conference and report on Family History. And to the founders of Geni.com, you missed on this one when Tindall presented to you. Or maybe you just are going to steal the idea.........

Congratulations President Obama

Now that we have a new president many may wonder what will occur in the realm of personalized medicine. Well, the short answer is ALOT. Several things that the democratic majority in the house, senate and executive branch plan to enact.

1. Senator/President Elect Obama's Personalized Medicine Bill will likely pass or Congressman Kennedy's version. What does that mean?

He has proposed an interagency task force on genomics research, modernize FDA review of genomics tests and expand support to genomics researchers, including funding and creation of a new mechanism to allow researchers across the country to access and analyze genomics research. As president, Obama will continue to support advances in personalized medicine to help ensure early detection and treatment of cancer and other diseases.

The bill appropriates $75 million a year to establish a National Biobanking Initiative and another $26 million to "Realizing the Potential of Personalized Medicine".

This means greater regulation in the field....including DTC testing. Too bad for Rupert Murdoch but we are actually going to require evidence for testing...

2. Increased funding for Personalized Medicine in Oncology
The Obama-Biden plan will help our health care workforce grow by expanding funding for loan repayment, adequate reimbursement, grants for training curricula, the Nurse Reinvestment Act of Title VIII of the Public Health Act, and infrastructure support to improve working conditions.

The Obama-Biden plan to double cancer research funding will also help recruit and retain clinical researchers who specialize in cancer by providing adequate funding for oncological study.

3. Obama will likely be having Francis advise him.... Can only mean good things.

The Sherpa Says: With an ailing economy, we need to invest in healthcare. It is the only resistant sector and it can lead us to better health outcomes.......

The Danger in Genetics

My great friend Adam Messenger just sent me an article which I can't believe I missed. Late June in the New York Magazine there was an article entitled "The Science of Gaydar"

Has anyone read this article? After I did, I was very frustrated....

From the article-

"If sexual orientation is biological, are the traits that make people seem gay innate, too? The new research on everything from voice pitch to hair whorl"

I do not remember a time when sexual orientation was classified as a disease.......However that is only because I am young. Ask a host of physicians and they will tell you that until 1973 the American Psychiatric Association viewed it as a mental illness along the lines with bipolar disorder.

"Back then, many psychiatrists treated homosexuality with shock therapy, detention, or a mind-twisting intervention called “aversion therapy”—a practice that was still in vogue in the late seventies, when a lumpy-faced psychiatrist put me through a regimen of staring at Playboy centerfolds."

The author talks about how classical morphology is being used to evaluate for sexual orientation. I feel this is almost as if they are discovering a new "syndrome". If you examine all first print literature of genetic syndromes you find much the same associations.

In fact there is a book that lists standard and accepted measurements for moprhology. This book used to be a mainstay for skilled clinical geneticists. There is another textbook called Smith's Recognizable Patterns of Human Malformation. The piece made me feel as if sexual orientation was soon to be listed in this book!!!! I am certain this will make the public feel similarly.

"A large-scale study within the next year is expected to determine more conclusively if a gene (or genes) is linked to sexual orientation. Alan R. Sanders, a psychiatrist from Northwestern University, is enrolling 1,000 pairs of gay brothers in one of the largest sexual-orientation studies ever undertaken. With the experiment, funded by an NIH grant of over $1 million, Sanders will attempt to map genes that influence sexual orientation."

This will create the first data in a long time on the subject. The Xq28 stuff is really suspect and I am certain there will be a much different take once this "study" completes.

But I agree with the author on his final assumption.

"It’s bizarre to think some value systems might lump gayness in with—say—sickle-cell anemia or Down syndrome. As Matt Foreman from the Task Force put it, “It’s not playing with the number of toes you have; it’s really manipulating your very essence. So many people see gay people only in terms of sexual behavior, as opposed to what sexual orientation is really about, which is how you fit into the world. I don’t want to get mushy, but it’s about your soul.”"

The Sherpa Says: What I have a hard time with is the simple fact that morphology analysis is being used. Even worse is the use of the term "gay gene" Yes genetics will impact everyone's life, but must we go at sexual preference. Aren't there bigger things to answer? Yes there should be some study of things considered deviant: child molestation, rape, etc. But I thought homosexuality was declassified in 1973......I guess I was wrong. If deCODE or any other DTC company markets a "gay test" please do not go out and take it!!!!!!!! Please!!!

More Than DeCODE found!!

In one of the most comprehensive evaluations of diabetes risk genes "researchers from the University of Michigan, the National Human Genome Research Institute, the University of Southern California, the University of North Carolina, and Finland's National Health Institute, have identified at least four new genetic variants associated with increased risk of diabetes and confirmed existence of another six.

The findings will be posted today in the online edition of the journal Science" This news was in Medical News Today. The findings include several genes which were not found by the DeCODE company. The Science papers confirmed six other genetic regions that others had previously identified as having a connection to type 2 diabetes.
Kári Stefánsson, the chief executive officer of deCODE, notes that a smaller sample size may help explain why his team didn't report two of the three new variants found by the three groups that pooled their data.
The story is not over for diabetes. I will maintain that any genetic testing being offered to the public right now is premature. We have replication studies. But what is really needed is analysis of a risk panel.

Dave Altshuler quoted in Science Now and the Gene Sherpa agree :"The findings are just the beginning of what GWA studies will accomplish, notes David Altshuler, the director of the program in medical and population genetics at the Broad Institute in Cambridge, Massachusetts, who helped lead one of the teams reporting results today. The next step is to sequence these regions and confirm the relevant genes. Figuring out how they work "is going to take great creativity and insight," says Altshuler, as will determining how and when to apply the results to patients." So would I run out to take the Direct to Consumer TCF7L2 test?...NO. It likely will just confuse the situation.