A new genetic testing tool developed by scientists at Harvard University and the Broad Institute can calculate a person’s inherited risks for heart disease, breast cancer and three other serious conditions. Investigators surveyed changes in DNA at 6.6 million places in the human genome and identified many more people at risk than do the usual genetic tests.

For example, of 100 heart attack patients the standard methods identified two people who have a single genetic mutation that places them at increased risk. The new tool found 20 of them, as reported recently in the journal Nature Genetics.

Debra Leonard, MD, PhD, talks to us about the latest advances in genetic testing and what it means for patients and families. Dr. Leonard is chair of Pathology and Laboratory Medicine at the UVM Health Network and professor and chair of the department of Pathology and Laboratory Medicine at the Robert Larner, MD College of Medicine at UVM.

What does this study mean for the field of genetic testing?

Leonard: Genetics classically started as one gene or one location in all of our genetic information being correlated with a particular disease. That has explained things like cystic fibrosis, Huntington disease, spinal muscular atrophy and other single-gene diseases.

Yet, many of the diseases that are so critical to healthcare, such as diabetes, cardiovascular disease and other chronic complex diseases are influenced by genetics. We know that because these diseases tend to run in families. There can be a family history, but we don’t necessarily understand how and why. It’s not a single gene causing that disease. It’s more like there are multiple genes that control your wellbeing or your disease state.

These genetic risk scores aren’t necessarily getting down to the specific genes related to a disease, but use markers across your entire genome that statistically relate to a disease risk, and they can pull out the ones for a certain disease that say you’re at higher risk of that chronic disease or complex genetic disease.

For example, there might be 40 markers. If you have 20 of those markers, then you might be at higher risk, whereas if you have only five of them, you wouldn’t necessarily be at higher risk. That’s what the Broad Institute and Harvard have discovered: five new genetic risk scores.

What’s interesting about this study is that these genetic risk scores have a lot of data behind them. They’re much more solid than some of the previous genetic risk scores in predicting individuals at risk for these diseases.

How does a patient interact with a tool like this?

Leonard: We’re hoping that these genetic risk scores will eventually become clinically useful.

Here in Vermont, we are focused on population health. That means keeping our patients as healthy as we can. What that looks like is anticipating what diseases individuals might be at risk for, monitoring them more carefully, or using preventive strategies to help them not get that disease. Or, once they have symptoms of the disease, to be on top of the right treatment right away.

So, instead of two out of 100 people who are at risk for a heart attack, if we could identify 20 people who are at risk of a heart attack of the hundred who are going to get a heart attack, then it gives us the ability to talk with them about healthy lifestyles and other things that they could do to lower their risk of having a heart attack, and possibly prevent or reduce their risk of a heart attack.

Who should get a genetic test?

Leonard: Right now, most of the genetic information that we use for patients is collected through family history. A family history tool is very important. If you have a strong family history of a disease, then genetic testing may be useful.

What’s interesting is that someone may want to know their risk of their family’s disease, but having a test is actually much more helpful to that person if someone in their family who has the disease gets the genetic test first. Then, we can identify the genetic difference in the genetic information that’s causing that genetic disease in the family. Then the person can see if they inherited that genetic difference and are at risk, or not.

We don’t understand everything about genetics, and so if you or I know that we’re at risk for a genetic disease, but we don’t know the causative mutation, we may have standard genetic testing for that disease, but there may be other genes not in that test that can cause the disease, and our family’s mutation might not be included in the test. So, we may get a false sense of assurance that we don’t have a genetic risk when really we haven’t tested the right gene and looked for the specific family mutation.

I know that sounds complicated, but very often the family member who has the disease getting tested first is the best place to start if a family member is interested in understanding their genetic risk.

How does that genetic testing change how a patient makes healthcare decisions?

Leonard: In general, when you have a genetic test done, you receive genetic counseling before and after the testing is done. The genetic counselor provides you with information about what we know about the genetics of the disease that’s relevant to you and your family, what testing can be done, and how complete that testing is in identifying people who have this disease, and can tell you the possible risks to your employment or insurance, other kinds of things. In addition to the federal Genetic Information Nondiscrimination Law that protects people from discrimination in employment and health insurance based on genetic information, Vermont and New York have broader laws giving greater protections from genetic discriminiation. After genetic counseling, you decide if you want the test or not.

What’s interesting is that in a population health setting we want to give individuals the choice to have this testing or not. That said, if it could help us take better care of a patient, then perhaps we need to encourage that individual to have the testing rather than simply saying, “It’s totally up to you.” So, genetic counseling is undergoing a bit of a changing paradigm.

What is an example of how a patient’s care might change, given genetic information?

Leonard: Lynch syndrome is a genetic disease that results in a higher risk of developing colon cancer or uterine cancer at an earlier age. When someone has colon cancer, then you could be tested for mutations in genes that cause this inherited risk of colon cancer and uterine cancer.

If you just have the family history of colon cancer in your family, then you are recommended to have more frequent colonoscopies than the general population without a family history of colon cancer. Colonoscopies aren’t exactly pleasant preps and procedures to have, but are very important if you have a higher risk of colon cancer.

If we know that you did not inherit the mutation that puts you at a higher risk, then you do not have to have colonoscopies more frequently, but only as often as everyone who does not have a family history of colon cancer. So, through genetic testing we can distinguish the family history from the reality of did you get the mutation or not, and if you don’t, then you can return to the frequency of colonoscopies that everybody else gets.

What do you see in the near future for genetics and genetic testing in Vermont?

Leonard: We are on a 10-year pathway to incorporate genome information into medical care in Vermont and northern New York. I came to UVM Medical Center and the Larner College of Medicine five and a half years ago as chair of the Department of Pathology and Laboratory Medicine. Part of my vision is to move us toward using patient’s genome information to inform the medical care that we provide. Shorthand, it’s “genomes for all.”

We have introduced cancer genome testing already. We are working on introducing pharmacogenetic testing that can tell us whether or not you’ll respond to a particular medication, do you need a different dosing of that medication, are you predicted to have a bad reaction to a particular medication, so we should pick a different one.

We are moving now to develop the clinical and patient pathways and workflows to begin genome sequencing for our patients. We will start with a thousand patients who will be invited to have their genome sequenced. We’ll provide patients with genetic counseling and ask for their consent for testing. Then, their genetic material from their blood will be sequenced and interpreted. Then, we will determine that the significance of their genome sequence for their clinical care. We will work with their primary care physician to provide that information back to the patient with genetic counseling support. From a genome sequence, we may have nothing to recommend, or we may to do additional testing, or we may recommend more careful monitoring, or referral to a specialist.

Is your DNA your destiny, or does a healthy lifestyle count?

Leonard: Whenever I get asked that question, I think about the movie Gattaca, which is is a society where your genome basically determines your entire life from the time you are born and even allows parents to choose the genetics of their children. In reality, no, your genome is not always deterministic.

Your DNA probably contributes 20 or 30 percent to your overall lifespan and health, but many other factors interact with your genetics. So, if you had genetics that said you absorb fats more rapidly than other people, if you eat a healthy diet and stay away from a lot of fats, then you would never become overweight. So there’s a lot of interaction. Socioeconomic status, education level, the healthcare we provide all contribute to your overall health.

Right now, though, genetics is a significant contributor to overall health, and we’re not routinely using that information for medical care. We now understand more about the genome, but we don’t understand everything.

Your genetic information doesn’t change, except with cancer, so after genome sequencing, we could keep going back to patients’ genomes as our medical knowledge grows, or as the patient develops new symptoms.

When I give talks on genomic medicine, one of my slides is a photo taken by my husband of a car on a Vermont road. In fact, it’s Pond Road down by Shelburne Pond. I point out that a genome is a journey. It’s different than other kinds of tests that we would do and need to repeat in the future. A genome is constant and we will keep going back to your genome information over time, as our understanding of genomes grows and as a patient develops new symptoms.

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