If a fortune teller had “read” my future two years ago, I would have learned that I was at high risk of dying. Soon. A year ago I was diagnosed with the disease that killed baseball legend Lou Gehrig. It’s called amyotrophic lateral sclerosis, or ALS, and mine is moving swiftly. I’d have wanted to know what was headed my way so I could start preparing for it and make every hour count.
What about you? Would you want a fortune teller to reveal your risk of developing something that might short-circuit the life you are living — heart disease or breast cancer or dementia — possibly years from now?
We are at the point where such “fortunes” can be told. I’m not talking about the kinds of genetic analyses done by 23andMe or Ancestry.com. I’m talking about something called polygenic analysis. This cocktail of genetics, high-end statistics, and advanced computer models, with a twist of epidemiology, measures the effects of myriad genes for a particular disease and distills them into the risk of that disease. All it takes is the DNA extracted from a sample of saliva.
I am a scientist who specializes in neurologic diseases. Seemingly by chance — but maybe by some higher power — I was working on the foundations of a polygenic score for ALS when I noticed one of my arms becoming weaker. Then my voice changed and swallowing became hard and, well, a fatal diagnosis emerged. I ran a polygenic analysis on my own DNA and learned that I carry several common ALS genes that also involve the immune system.
This information gives me something to do about my condition: try immune therapies that just might slow the progression of my disease.
For most people though — perhaps for the vast majority who don’t have ALS or some other potentially fatal disease lurking in the near future — is a polygenic analysis useful?
I think it is. Personalized polygenic scores can help individuals understand their risk for dozens of conditions, from Alzheimer’s and heart disease to schizophrenia and lung cancer. These tests are slowly being commercialized. You can go online and order a polygenic report card for breast cancer from Myriad Genetics or one for Alzheimer’s disease from Dash Genomics. But keep in mind that some of these tests have not been rigorously evaluated because the medical community is still trying to figure out how to incorporate polygenic scores into clinical practice.
One of the most important things to know before ordering this kind of test is that a polygenic score is not a diagnostic test. It measures your risk for developing a disease, not whether you do or don’t have it or will ever get it. Such risk information can be remarkably helpful. If you are at increased risk for heart disease, getting serious about lowering your cholesterol and exercising more could keep it at bay. An increased risk for breast or prostate cancer could translate into beginning screening earlier in life.
Polygenic analyses may also pinpoint effective treatments for diseases like ALS. One reason why drug trials for ALS continuously fail is because the treatments are tested on individuals who have little in common except this diagnosis. Polygenic scores could help match a drug that has a particular effect to people who would most likely benefit from it. A trial of an immunotherapy drug, for example, might give more bang for the buck by focusing on individuals who have high immune polygenic scores.
Uncertainty is a hallmark of the polygenic score. But this uncertainty leaves room for action. Behavior is as important as genes in setting the stage for your future health. That means healthy changes in behavior and lifestyle or therapeutic interventions can prevent or modify the trajectory of disease and will likely be good for you regardless.
Today, polygenic scores are a blunt instrument for predicting disease risk. Down the road, combining them with other clinical factors and measures of disease risk will make them more effective.
Ordering a polygenic test means you want to know what may lie ahead and are willing to make changes if needed to alter the story told by this genetic crystal ball. If not, you might as well use the money you’d spend on the test to have a great meal at your favorite restaurant.
Two years ago, had I been given even a tiny hint that my genes were tipping the scale for the development of a disease that would lock me into my body, unable to move or breath normally on my own, I would have been sad, and probably mad. But then I would have packed more hours into developing genetic analyses to help people solve diseases like ALS. So now I’m running as fast as I can — from my wheelchair.
Isn’t this what most of us want: to see the best future for ourselves by taking control of our destiny?
Rahul Desikan, M.D., is an assistant professor of radiology and co-director of the Laboratory for Precision Neuroimaging at the University of California, San Francisco.
Yes, genes plays major role in diseases. When there is no family history of a disease in few generations, by seeing into genes we know what got mutated or what got expressed..but how do we know what triggered that? Are we looking in wrong place for clues?
I am a patient and I can not travel because of pain I have to be in AZ every month I am81.
What worries me is being able to determine risks of future problems preterm. The classic example is trisomy 21. How often does a mother find out the child she is carrying has an extra 21 chromosome and decide to terminate? I guess Huntington’s would have the same issues as ALS. Sometimes it might be better not to know.
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