01/30/2010 On Genetics and Us

I was once cornered by an individual who began firing off questions about personalized genomics. He had done his research. "Do you know how many conditions companies like "23 and Me" can test for?

"No.”

"Now I read that all of us are carriers of at least 7 or 8 recessive genetic conditions. Is that true?”

"Yes.”

"Well, how do they know that is true? Have they tested everyone? Do they revise that number over time? Have they tested the eskimos?"

Anyways, this went on for several minutes, but the topic is one that I have found particularly interesting since grad school. Now, I am not as much interested in WHAT these new personalized genomics companies have to offer. Rather, I am more interested in people's responses to learning that they could potentially have access to this very personal genetic information.

Here's the deal. When we think of "genetic disease, " we frequently think of what we call "single gene disorders. " One gene has a mutation, and that mutation leads to that individual being affected with a genetic condition. One gene, One disease. Sickle cell disease. Duchenne muscular dystrophy. Cystic fibrosis. You get the picture.

Over time, we are learning that the majority of conditions and diseases do not fit into the "one gene, one disease" category. Rather, these fall into the category of multifactorial disease, which means that there are likely many, many genes, and many, many environmental factors, that all interact with each other. Line up certain genetic variations with different environmental prompts, and you have a complex multifactorial condition. Lupus. Multiple sclerosis. Type II Diabetes. Parkinson's disease. Several direct-to-consumer companies have developed genetic testing that can be ordered from a private individual's home and sent directly to a lab with no doctor involved. Some of these companies have genetic counselors, others do not. Some of these companies help their customers and their customers' physicians interpret their results, others do not. Several of these labs do offer testing for single gene conditions on their panel. In addition to testing for known single gene disorders, many direct-to-consumer companies also offer risk assessments for common complex and multifactorial diseases. A big area of research at the moment involves trying to locate variations in our genes, or polymorphisms, that could confer an increased RISK for a condition. What this means is that this polymorphism, in conjunction with other genetic and environmental factors, could lead to disease.

As you can imagine, the confounding variables in these studies are numerous (for example, did this polymorphism influence this disease, or was it that this individual lived next to a tire manufacturing plant for 30 years? ). There is still much to learn in this area, and many feel that we're far away from giving accurate risk assessments for individuals based on our current limited knowledge of the diseases that affect people today.

Here is what interests me. Many people, probably including the individual I mentioned above, would be a kid on Christmas morning if they could get their hands on their own personal genomics report. To be able to say, "well look at that, they found that I carry a risk factor for heart disease" holds great value for many. But what will they do with that information? In grad school, we had several discussions about where the health focus should be in today's society. We all support the research and advances that have developed over the years in treating single gene disorders and the testing that has allowed other family members the ability to know if they are at risk. But what are the greatest concerns for the health of people in developed nations in this world? The modern lifestyle that has brought us so much has also been dangerous to our health, despite the amazing health care gains that have developed over the past 100 years. There are numerous medical conditions that affect low-risk individuals for reasons we do not understand. However, for many of us, our risks for disease would decrease significantly if we were to change our daily habits. It is difficult to leave the comforts that bring us pleasure, like smoking, the sedentary life, and food.

I took some very eye-opening courses in the Public Health Department when I was at U of M, where the discussion focused on helping individuals to address their ambivalence over change. We learned about identifying the personal barriers to change, and what small steps could lead to minimizing those barriers. The bottom line is that change can really, really suck. While direct-to-consumer genetic testing companies advertise the benefits of knowing if one carries an increased genetic susceptibility to multifactorial diseases, we as individuals may not understand that our greatest control in our health lies in our behaviors. That is what concerns me. So what if you carry a polymorphism present in 5% of the population that is thought to influence one's risk for hypertension. Is that going to get you to drop those 30 pounds and adopt a healthier lifestyle? You tell me.