We need more Samples/Sherpas!!!

Genetic Research is a hard business. You have to fight and IRB to get your I's Dotted and Your T's crossed. You have to write and write and write grants to get funding for your ideas. You have to manage the project and work to keep everything on track. But what will the rate limiting step be in genomic research?

Perhaps it is the lack of samples?

From Medical News Today, an exciting announcement regarding Lupus. Lupus is a terrible disease where the immune system attacks the body's DNA. It can cause horrible things including, stroke, skin disease, kidney disease, brain inflammation. In fact a whole host of persons who have this disease are unable to function in society.

A new finding includes the discovery (Not Validation) of a gene implicated in Lupus' pathogenesis (disease cause) OX40L. These researchers have identified other risks as well. His findings are only mildly interesting as replication will be needed. But what is more telling is his plea to the British people

"Without DNA samples from people with Lupus, we would be unable to study the disease," he says. "Despite the disease being relatively common, DNA samples are in short supply. I would encourage patients to discuss with their GP or consultant about providing a blood sample to help further our understanding."

With all of these companies looking at your SNPs or your Exomes or your Genomes and the vigor with which they launch PR campaigns. One would hope they could donate their datasets to these Scientists in need.

I perosnally have been trying for months to help a friend donate her genome to a sequencing project. Hope fully the Delaware Valley project will take her code. I think that genome sequencing will ultimately win the day over some of this SNP Chip technology. Why? SNPs are not enough. Copy Number Variation will slowly be found to play as large a role...if not more. You can read about some of this here.

The Sherpa Says: Did anyone watch the 60 Minutes special on Sherpas in The City. Turns out that for their health Sherpas are moving to New York. Any Gene Sherpas in the batch? I sure hope so. The Gene Sherpas of the world are coming together for one big collaboration and I can't wait till we all can guide the genomic tourists of the world!!! Stay Tuned for the Sister services soon to show up on the scene. Heads Up L.A., S.F., CHI!!! Are you a Sherpa? Want to join the team? We would love to have you. Can't wait to see you all in NY!

18 Hours to Vote!!!!

Lots of things have transpired since Sunday. I would like to say first, sorry for no posts since Monday. I was preparing for my presentation at the Connecticut conference for the American College of Physicians. Second, I need more submissions for the Genie this weekend. I will be hosting my second and am looking forward to reviewing some great posts. Third, Navigenics is ready to unleash its technology on some unsuspecting consumers in '08. I know at Helix Health of Connecticut we are ready for the wave of "What does this mean?" "What should I do health wise?" etc.etc. etc.

In fact,

We just received a call from a wonderful consumer of the so-called SNP market for nutritional supplements. The big problem here is that there are SOME SNPs which actually predict risk for disease. But what do they get for a report? Eat more broccoli...Thanks.. I am scared that they don't understand about these "genes" really being a part of your medical record. Because some are as strong as a cholesterol panel in their ability to predict risk. The even bigger problem, most are not. And what happens when Navigenics gets out over the skis and says that they are? Who will be left to pick up the mess???? The fewer than 1000 geneticists? The PMDs who don't even have the training to comment on this? This is one of the major reasons why we are reaching out to educate PMDs.

I have a concern with Whole Genome Sequencing.....it really is just a snapshot in time. I emphasize the role of continuing evaluation of expression and epigenetic effects. Luckily, USC just received a bundle of dough to research and evaluate epigenetics. This is a great reason to have a continuity of care with those who have seen and attempted to interpret your genetic data. We can't keep bouncing this reductionist idea of "If we just have your genome, then we can help you live forever and cure all disease" at the market. This is what Francis Collins would call "Overselling the technology" Please answer my poll question "How much would you pay for the oversold genome?" Oops, I mean "The cutting edge achievement know as the Human genome. You should get yours done too."

I was warned by a friend of mine. He said "Shooting from the hip and having no planning of your posts is ONE WAY to blog. Another would be to plan and deliver a message." I say, why not do both. There is more than enough foolishness going on to point out. Let me know what you think.

While giving the talk today I was asked about how we can get physicians up to speed in genomics. I stated "We cannot, we have missed the boat. We were warned in 1993 and again in 2000. Medical schools never picked up the slack. Too few clinical geneticists in the basic sciences. Less than 40 Medical schools have defined courses in genetics. Up until the last few years it wasn't even a prerequisite for medical school. See the Banbury Summit. How can we teach those who never learned the language? Only one way, complete and total immersion. Much like how an adult learns a language. I have used vignettes that have clinical applicability. Unfortunately, this takes at a minimum 2 years to see any effect. If we were to do this today we might be able to make some inroads"

But physicians will not be ready for Navigenics. Boy, it sounds like this is an argument for "Direct to Consumer and Navigenics report based medicine" Well it is not why? What physician delivers care without a physical exam? One who is looking to get sued, that's who. Good luck to all the report makers. I hope you have an army of attorneys because malpractice coverage will not be enough.

The Sherpa Says: Thank you once again to Genome Technology Online I am very happy that they enjoy my musings. I hope my CGC friends did not get the wrong ideas. I am not bashing them, I am bashing the system. A system which I hope you will join me and fix.

About Helix Health of Connecticut.

Well, I have been getting alot of questions regarding our personalized medical practice on Park Avenue in New York City. I have been reluctant to tell everyone, but I figure that I might as well let everyone in on our "secret"

My philosophy is the power of genomics should empower patients and providers. Together as a team we can prevent some horrible diseases and avoid some horrible adverse drug reactions. How do we do this? We take the skills from a multidisciplinary team and identify risk. We feel that the most powerful genomic tool out there is family history (Sorry Hsien). This has been validated over and over again in epidemiological studies.

In fact when Mike Leavitt indicate in his foreward of his Personalized Health Care report

"One part of the foundation for such a change is our rapidly growing understanding of the human genome and the processes it directs. We envision health care that could:

• predict our individual susceptibility to disease, based on genetic and other factors;
  



• provide more useful and person-specific tools for preventing disease, based on that knowledge of individual susceptibility;
  



• detect the onset of disease at the earliest moments, based on newly discovered chemical markers that arise from changes at the molecular level;
  



• preempt the progression of disease, as a result of early detection; and
  



• target medicines and dosages more precisely and safely to each patient, on the basis of genetic and other personal factors in individual response to drugs. "

I thought he had read our business plan. But then I realized, anyone with an insider view would have to conclude the same thing. This IS personalized medicine. I think that the fields we will see explode are services which Helix Health of Connecticut is offering.

The problem I have always had with academic genetics is 3-fold.

1. Most geneticists are pediatricians (8 in 10) and have not been trained in adult chronic diseases or even used most medications that are intended for adults.
   
2. Traditional genetic care offered in the "Ivory Towers" is diagnose and adios. They have no desire to offer close follow up. In fact, in the time that I worked at an academic center we did very little to recontact those difficult clinical genetics cases. Only metabolic patients get the close follow up needed.


3. There is NO privacy at a big center. In most places you are pushed through like a means to an end.
   

The last problem I have with traditional genetics lies in how we acquire medical information.

In a clinical genetics appointment of 45 min to 1 hour you get a fam hx from the genetic counseling student which takes 20 minutes, they attempt to take a medical history (despite having no medical training), they then present to an attending or fellow (10-20min), who then comes in a confirms the information. Now with 15-20 minutes the attending has to explain complex genetics and inheritance to you, send off subtelomeric, CGH, karyotype, genetic tests, etc. And you get ONE follow up appointment and may wait 6 months for another appointment.

In a cancer genetic situation you do have more time. Perhaps if your counselor is good, you get adequate follow up and acquisition of information. You may be seeing a geneticist (Who has not trained in adult oncology) or you may be seeing an oncologist (Who never trained in genetics) If you even see a physician at all. This is not to knock my CGC friends. They have truly great talent and training, but learning what to do with your Plavix is not one of them. In fact our head counselor said "When I took a family history and it looked like there was early heart disease I said to myself 'I know something is there, but what do WE do about it?' Therefore the problem lies in the training or perhaps in the team.....

And please do not get me started with the Chop Shop known as "prenatal genetics/high risk OB clinic" Where the standard is to get as many people as possible into and out of the counselors office and the into and out of the amnio as quickly as possible. Where is the CARE in that? Is there any PRE-Conception care out there? There is at Helix Health of Connecticut!

What kind of medical informatics system is employed at most academic centers? Archaic at best in most. At least where I and my partners have been. When even the highest powered EMRs cannot distinguish between maternal or paternal lineage, then you have a problem. We have developed our own.....

Lastly, where is pharmacogenomics? Where is chronic disease risk stratification? Oh I forgot, geneticists don't do this, nor is there training for this in classical genetics fellowships.
All of this and more is available in my vision of what personalized medicine should be. Helix Health of Connecticut is Personalized Medicine for the 21st Century(TM)

The Sherpa Says: Helix Health of Connecticut of CT is my dream, my vision and the tip of the personalized medicine spear. I know this may seem like an advertisement, it is not. It is the road map which all personalized medicine practices should follow. When you take Prediction, Prevention and Privacy to the highest standards of care, you are bound to succeed.

Want Longevity? Quit smoking and eat less.....

Yes, quitting smoking and eating less can help you. But it turns out some people will have an easier time doing these things. Also of note we begin to prove Murphy's Hypothesis (There is no such thing as a mongenic disease) These recent genetic studies caught my eye last week.

The first of this is sentinel study (Warning, all sentinel studies require replication)
This study reveals that patients with changes in the Cytochrome P450 enzyme 2B6. It turns out that"individuals with the CYP2B6 6 allele of the gene benefited from bupropion treatment and maintained abstinence longer while doing poorly on placebo, with a 32.5% abstinent rate vs. 14.3%, respectively. In contrast, those in the CYP2B6 1 group did well on both bupropion and placebo, with similar abstinence rates at the end of treatment and after a six month follow-up"

True that we do need some replication on this one, but there does seem to be other literature indicating this trend and other polymorphisms in Dopamine Receptors as well.

In addition to this one an article came out in AJHG this week. I want everyone to give up these words "MonoGenic Disease" Why? There is no such thing as a monogenic disease, unless you only have ONE GENE in your body. An example of this dichotomy is seen in the MONOGENIC DISEASE Hemochromatosis (Which BTW is not monogenic)

Unfortunately most Hemochromatosis is caused by mutations in HFE, but despite this testing, there are still people with Iron Overload who do not have HFE mutations. This is why I am not an advocate of HFE screening or even DTC testing of HFE. Even crazier, different people with hemochromatosis present differently. Why? Because there is no such thing as a MONOGENIC disease!!! In the AJHG this week an article shows that common variants in 3 other genes affect the penetrance of hemochromatosis. These genes are BMP2, BMP4, and HJV.
Serum ferritin levels were all affected by these common SNPs.There was even some indication of synergy between genes. To translate-Hemochromatosis is a multigenic disease, which primarily has problems in the HFE gene. So now is that clear as mud? The point....Don't expect a DTC test for hemochromatosis to tell you 1)If you will have Iron Overload 2)How bad your disease will be.

Finally, before you fall asleep or your heads explode, I want to chat about longevity. Some people think longevity can be bought with hormones, others with vitamins and Nutraceuticals (actually there is better data here). One big group thinks that all we have to do is stop eating.

This starvation group has recently been vindicated by studies on a family of genes called Sirtuins. A recent review was written in the Annals of Medicine. But just a couple of days ago an article in Cell the guys from Harvard Path publish on the role these genes play. Warning. This is a science heavy paper and the clinician may not find it useful at all....Dr Hsien Lei actually posted on this article as well. I see this as a potential windfall for companies looking to create Sirtuin activating cereals..........

The Sherpa Says: Gene Genie is up at Neurophilosophy so check it out! I am tuning up to host the next! We have along road ahead of us.....I like the way we are headed. However, there are some big bumps and changes coming up. Let's all keep our eyes on the prize...Truly Personalized Medicine

LRP8 and Familial MI....Ho Hum

This month in the American Journal of Human Genetics we have some interesting publications. Including an association study identifying a gene known as LRP8. So what is LRP8? It is a receptor for bad cholesterol. When bad cholesterol binds this receptor, platelets (the bricks in your blood that build a clot) become sticky making it easier to thrombose (form a clot).





I am interested in this study for several reasons. First, it has been shown that platelets get stick even after ingesting a Big Mac. That's correct. Just one fast food hamburger can theoretically precipitate a heart attack. So naturally we would love to know who. Think Personalized Diet/Nutrigenomics. I wonder if Salugen can hear me now? I still haven't received their "Scientific Data" yet. I will publicize it if they do.





Back to the study. So what was studied is a group called the GeneQuest families of familial MI, the control group was some white men who were given cardiac catheterization and found to have no atherosclerosis burden (OOPS). Well, that control does not mean they did not have atherosclerotic burden, because catheterization cannot identify 30% occluded vessel plaques.





In addition their findings were replicated on an Italian cohort of familial heart attack as well. So why do I say Ho Hum?





Let's see: No Odds Ratio was greater than 1.43 This 43% increase in heart attack and coronary artery disease is still less than the family history risk itself. The only good thing was that this risk persisted even when controlling for plasma total cholesterol levels, triglyceride levels, hypertension, and diabetes, in addition to age and sex.





What is your odds ratio for heart attack if your father had one prior to 65?


The Answer: 5.8 according to Maren Scheuner's article on familial risk for MI.





Do you now see why I say HO HUM about this gene? When will we see the gene card panel for MI??????

The Sherpa Says: Listen to all of this hulabaloo about Ventner's Genome. Even Men's Health magazine says you should bank your parents DNA if they die. What good is all of this if we don't have a key to the map? The map will make no sense! LRP8, APOE4, I could go on and on. What good is a genome map, without a guide? What good is the guide without the studies? Why did you buy the iPOD early, only to have late adopters get it cheaper? For the rebate? Doubtful. This is why primary care physicians are late adopters. If you want to get your genome (and I do) then you better be prepared to find someone who will help you understand it...becasue cliff notes, or Navigenics just won't do. Nor will scarfing down Big Macs....