The Impact of My Genetic Testing on My Father

Abstract

Twelve personal narratives address the challenges, benefits, and pitfalls of genetic testing. Three commentary articles explore these stories and suggest lessons that can be learned from them. The commentators come from backgrounds that include bioethics, public health, psychology, and philosophy.

As a clinician and genetics researcher, I was excited to get my personalized genotyping and report from 23andMe. Silly as it seems, I didn’t think twice about how these results would impact my family.

Prior to testing, I was concerned that I might have one of the genetic variants that cause breast cancer, because prostate cancer runs in my family and there are some genetic variants that contribute to both prostate cancer and breast cancer. Therefore, I was relieved to see that I am not a carrier of a high risk variant for breast or prostate cancer.

Surprisingly, I found out that I have an APOE4 variant, one of the strongest genetic risk factors for Alzheimer’s disease. This was particularly surprising because no one in my family has died of or with dementia. In addition, my paternal grandmother is 99 years old without dementia, and my maternal grandmother is 100 and only developed cognitive impairment from a stroke at age 95.

Outside of testing for specific genetic variants that cause relatively rare diseases or testing of tumor tissue to help guide cancer treatment, my “expert” opinion is that genetic testing for health risk is almost purely an intellectual exercise. Results can be used for medical care in a similar way to knowing family history, except these generalized genetic results are much less informative than even the most cursory family histories. Specifically, knowing that my patient has a father with hypertension and had a heart attack at age 60 is more clinically useful than knowing that my patient had a 23andMe test that reported “elevated risk” of heart attack.

The relationship between Alzheimer’s Disease and APOE4 is an exception to my opinion. Alzheimer’s Disease is not a rare disease, and APOE4 increases your risk for Alzheimer’s Disease, but it is not deterministic. Strong medical research shows that, if you have a family history of Alzheimer’s Disease, you have a much higher risk for Alzheimer’s Disease, if you have the APOE4 variant than if you don’t. In addition, there is evidence that APOE4 increases your risk for Alzheimer’s Disease even without a family history. Basically, knowing that my patient has the APOE4 risk allele is a clinically useful piece of information whether or not there is a family history of Alzheimer’s Disease.

Currently, we do not have treatments for Alzheimer’s Disease, although rapid advances are being made in understanding the biology behind Alzheimer’s Disease and I am confident that there will be effective treatments or preventions for Alzheimer’s Disease within the next 10 to 20 years. From my perspective, even though there is no treatment or clear prevention, knowing that I am at high risk for Alzheimer’s Disease is helpful for my own future planning.

This also significantly impacts my family. If I carry the APOE4 variant, at least one of my parents does as well. Within an hour of receiving the results, I called my parents, who are in their late 60’s. Despite my medical experience and training in genetics, I was unprepared for the consequences of this phone call.

My father is a statistician in all senses of the word. He has a doctorate in statistics, and his entire career included statistical analyses of large databases. More unusual, he quantifies and analyzes most aspects of his life including (but not limited to) precise sleep hours, heart rate during exercise, dietary fat and cholesterol (starting in the 1970’s, well before it became popular). Therefore, he went through my complete family tree and determined that, although there has been no Alzheimer’s Disease or dementia that we know of, because his relatives have died at younger ages than my mother’s relatives, the APOE4 variant must come from him. He does not even speak of it as, “there’s a good chance that I carry the variant”, he states that definitively he carries the variant. At one point, I suggested that he get confirmatory testing, but he deemed that unnecessary because it is certain that he has the variant.

He changed his life immediately—he retired from his job, moved, and sought out investigational treatment for Alzheimer’s Disease. My decision to get genetic testing and communicate the results is responsible for these life changes.

Now, three years later, he shows no signs of Alzheimer’s, and he seems less driven by concern for his imminent cognitive decline. However, I cannot overstate the significance of my genetic testing on almost every decision he has made since I was tested.

My own feelings are highly conflicted. First and foremost, I am the cause this concern. But I feel strongly that it is not my fault. Although I had genetic testing, I am not responsible for my own results and I did the right thing by communicating these results to my parents. If he does have the variant (which is probable but not definitive), he made reasonable decisions to focus his life on moving forward with projects that are meaningful to him, and physically moving to be close to family in retirement. What is upsetting to me is that this experience has made him blind to the probabilities he so thoroughly understands: he does not acknowledge that he may not have the variant, and he does not acknowledge that, even if he does have the variant, he may not develop Alzheimer’s. I wonder how things would be different if I never had been tested. Would he have found something else health-related about which to be irrational?

Several years ago, the FDA effectively shut down the health-related component of 23andMe, stating that the health-related information given was acting as an unapproved medical device. Although you can pay $100 to receive an extensive genotyping, the interpretation of these data is limited to a comprehensive ancestry report.

I firmly believe that we should be increasing access to genetic and other medical information rather than decreasing access, despite the fact that the medical implications most of the information is unclear. However, it is clear to me that my father’s path, and by extension my family’s path, has been dramatically altered by my decision to get myself tested.