Three cases first:
A young woman I met recently (outside the hospital) told me her Dad died suddenly a couple of years ago. He was fine, then he was stone cold dead. The wife went outside for a minute and came back to find her husband dead in the chair. There were no warnings. No chest pains, no breathing problems, and no real diseases, except well-controlled high blood pressure.
A middle-aged man came to see me in the office because his brother died suddenly while jogging. The patient wanted to know his risk of heart disease and what he could do to prevent premature death. Both my patient and his dead brother were in decent shape.
Finally, a well-educated patient, who did not have heart disease, asked me about the decision to take statins. His primary care doctor recommended the drug based on his cholesterol level plus his age. This man had read the studies showing only modest benefits for statins in primary prevention.
*****
Gene Risk Scores
My most recent column over at theHeart.org | Medscape Cardiology delves into the use of genetic data to help predict heart disease.
I know; writing and reading about genetics is akin to eating broccoli instead of pizza. Give me leeway for a minute or so, this is nifty stuff. I learned bunches.
First some background: We now know there are many gene locations on our chromosomes that associate with coronary artery disease. At these areas are many single nucleotide changes, called SNPs, or single nucleotide polymorphisms, that may individually or together influence the risk of getting heart disease. SNPs sound tricky but really they are just a single substitutions of say an A for T or G for a C in the DNA.
In recent years, researchers have been able to cull these many SNPs into a composite score, called a GRS, or gene risk score. Companies like 23andMe used to report gene risk scores for heart disease but the FDA asked them to stop. (That’s probably coming back soon.)
My point is that these gene scores are not pie-in-the-sky stuff.
Now to the compelling evidence. In the Medscape Cardiology column (you need to give your email to read), I review the numerous studies of using gene risk scores to predict heart disease. It can be summarized into five main points:
- Gene risk scores are not just a fancy family history. The score predicted heart disease independently of self-reported family history. The obvious weakness of a self-reported family history is that people live different lives from their parents.
- Gene risk scores can predict different trajectories of heart disease risk. If you plot survival curves of low genetic risk versus high genetic risk people, the people with high risk scores get heart disease at a younger age.
- Genetics may help pinpoint those individuals who may benefit most from statins. I cited multiple studies showing that individuals with high genetic risk garnered much greater risk reduction from statins than did those with low genetic risk. This is really cool. The researchers actually used blood from patients in the randomized controlled trials for statins to show these gradients of benefits.
- Gene risk scores may influence people to change behavior. I also cited studies showing that people with high genetic risk who pursue healthy behaviors can reduce the chance of a future event.
- Gene risk scores have advantages over imaging tests such as coronary artery calcium. For one, CAC depends on age. Gene scores can identify young people at risk. Another advantage is that gene scores are a simple blood test rather than a scan.
I hope you read my column on theheart.org | Medscape Cardiology: Who Needs a Statin? DNA Beats Current Risk Calculators. The reference list of studies is there.
In the column, I cite work that Dr. Eric Topol and colleagues from Scripps are doing. They are in beta-development of a free-mobile app that takes a person’s 23andMe data and churns out a risk score on your phone. It’s called MyGeneRank.
Your doctor can’t easily order gene risk scores now. Insurance doesn’t cover them. But the tests are not too expensive. My prediction is that soon enough, knowing your gene risk scores will be like knowing your LDL–only the gene data will be far more useful.
JMM
P.S. I needed a lot of help to learn this stuff. Dr Pradeep Natarajan of Harvard deserves a shout out for taking the time to explain much of this to me. You can follow him and his mentor Dr. Sek Kathiresan on Twitter.
Dr. Eric Topol, who is editor-in-chief of Medscape, a famous cardiologist and now genomics researcher also helped me learn this material.
Joan says
May 5, 2017 at 10:54 amThanks so much for this Dr. John. I’m glad I lived long enough to see genetic science blossom and become productive and life-changing.
I am also fascinated by the evolving research into the human gut biome, which apparently is in the driver’s seat for many of our basic functions, even our moods. All those trillions of little critters living inside us might be an even more potent health determinant than our genetics.
Me says
May 5, 2017 at 11:46 amSome points. 23andMe uses saliva, not blood for testing. That is why you can do the test at home and mail it in.
They now have FDA approval to include genetic risk reports starting in April 2017. Promethease for a long time has used the raw data file from companies like 23andMe and, for $5.00, gives more detailed and complex genetic reporting. The real question is – do you really want to know some things?
23andMe does make you click a button at their website to see genetic risk reports for parkinson’s or alzheimer’s diseases. But really, it’ll keep haunting you until you do look at results. There is no un-do button. Promethease gives you the full reporting without a warning. There are filters to control what you see, but it is all there (for what is available today).
Understand why 23andMe at least has you click that button before viewing your genetic risk for these two diseases. Well-known scientists have asked not to receive info for these diseases when doing their own genetic testing. These diseases are NOT LIKE cholesterol where you can take a stain that can make things better. There is no “better” for you with the two mentioned diseases that are so destructive.
Yes, many related genetic and other factors are still unknown in how they might influence outcomes. And you may reduce risk by factors like life style. Treat risks like high total cholesterol, high blood pressure, obesity. Stop smoking. Exercise. Eat a Mediterranean diet. Sound familiar?
You make it sound like knowing genetic risks is all good so you can deal with problems early. But knowing genetic risks might not be useful at all for some. You may, or may not get a devastating disease, you don’t know if or when something will occur that will greatly harm you.
Dr John says
May 5, 2017 at 12:03 pmThese are thoughtful and useful words.. Commrntary like this makes me glad that I did not close comments.
I agree with you.
I think the researchers used blood to do their study. But you are right about 23andMe and saliva.
I made the point–strongly, I hope–in my Medscape piece that GRS for CAD may be exceptionally valuable because CAD is so modifiable.
Anthony Pearson says
May 5, 2017 at 12:46 pmJohn,
Well done article at Medscape. I saw the referenced article when it came out and have to say I was underwhelmed. I still think that searching for subclinical atherosclerosis via coronary calcium or carotid plaque, i.e. seeing if the patient has the phenotype, is superior to the current risk factor assessment with or without genotype information.
Your article and above comment triggered me to go back and look at my 23 and me data (which includes nothing about cardiac risk) and I found I have a “slightly increased risk of late-onset” Alzheimer’s disease.
Great! One more thing to worry about.
Thanks
Anthony
Andy Miller says
May 5, 2017 at 9:57 pmDr John did you do the easy test check for Prolonged QT on the dead man’s brother?
Dr. György Báthori says
May 9, 2017 at 4:00 amDear John,
My congratulation. It was again a great and important post. Just to emphasize the importance of the post I would like to add some further notes:
Due to the NGS technology the progress of the application of nucleic acid sequencing is incredible fast. The hegemony of the genome wide association studies (GWAS) is now over. Gene coding fraction of our DNA is less than 3% of our total genomic material. Exome sequencing is narrowed our interest to the coding regions. But it is not end of the story. Concerning the cardiac diseases the diagnostic gene labs can offer disease specific cardiac panels. But the research can expand our horizon further. In the near future likely we can give more accurate predictions for instance for the stroke risk of afib patients from the gene variants of appropriate set of genes. Basically this is the DNA world. But it has limitations. Genes might be expressed or not. The genetic background of our pathological problems are usually polygenic. The DNA sequencing can give information only on odds and chances. From DNA data we can’t tell what really happens. The new opportunity for clinical testing is the world of microRNA (miRNA). From miRNA profiling of simple blood samples likely we shall get accurate data on HCM progress, statin sensitivity or afib generating remodeling of our heart.
Kind regards:
György