An ambitious vision for personalized medicine has become a reality, as the case of Pam Dyer illustrates.

The vision of a decade ago was to generate genetic data from UCHealth patients who agreed to participate in the biobank at the Colorado Center for Personalized Medicine (CCPM), a partnership between UCHealth and University of Colorado Anschutz Medical Campus, and then use that data to identify specific genetic variants that could increase the risk of cancer, heart disease, and other health problems as well as issues with how patients process a variety of medications.

The reality for Dyer is a much-improved outlook. She’s an athletic 65-year-old in Fort Collins whose biobank-driven diagnosis of a rare genetic condition led to faster treatment than would have been otherwise possible.

Dyer is one of more than 235,000 patients who have consented to provide a blood sample since the biobank launched in 2014 with a $63 million investment from UCHealth and its Anschutz Medical Campus partners. Of those, more than 135,000 and counting have provided samples to the biobank for analysis, and nearly 22,000 have received information about how their genetics may affect either their health prospects or their metabolizing of medications – that’s called pharmacogenomics, or PGx.

Dyer, who works in a biochemistry lab when not working out, walking, biking, paddleboarding, skiing, and doing other active pursuits, was enthusiastic about enrolling in the biobank.

“I love genetics,” she said.

Little did she know that her contribution to the CCPM’s wide-ranging research program would return the favor.

Biobank finds a genetic variant with consequences

Starting about a year ago, she just didn’t feel well. She wondered if the fatigue and the heart palpitations that would go on for several minutes had to do with aging. But when she passed out on a walk, it became clear that something else was going on. She was undergoing tests guided by her primary care physician, Dr. Stace Fritzler, when she got a phone call from Emily Todd, the lead genetic counselor at the Colorado Center for Personalized Medicine (CCPM). Todd said the biobank’s analysis of Dyer’s sample had found a genetic result that could affect her health. Would she be interested in learning more?

As of late September, Todd and colleagues had made over 350 such phone calls to patients whose biobank samples had genetic variants that boost disease risk and also have treatments for those diseases. The list of genes the biobank analyzes is based on recommendations from the American College of Medical Genetics (ACMG), says Kristy Crooks, PhD, the CCPM biobank’s director. That’s far from an exhaustive list of protein-coding human genes – they number about 20,000 – but it includes many genes associated with cancer risk, cardiovascular risk, and other conditions such as hereditary hemochromatosis. The list has grown over time and should continue to develop as medical researchers establish more and more gene-disease connections, Crooks says. One of the genes in that list is TTR, which can cause hereditary transthyretin (ATTR) amyloidosis.

A genetic variant in the TTR gene may be benign – or it can trigger the production of sticky amyloid protein clumps that can gather in the heart and the nervous system. ATTR amyloidosis disproportionately affects people of color. The biobank made a point of looking for it.

“Part of my motivation is trying to help level the playing field in terms of access to genetic information,” Crooks said. “One way we could do that was by prioritizing TTR.”

Dyer is not a person of color, but when she told Emily Todd that she indeed would like more information on the result the biobank discovered, it turned out to be TTR.

Biobank’s disease risk discovery prompts medical options

The biobank’s job was not done. Once a disease risk result is discovered and the patient asks to learn more, the biobank creates a clinical-grade genetic result that is shared with the patient and their providers. Fritzler referred Dyer to Dr. Amrut Ambardekar, a University of Colorado School of Medicine cardiologist with expertise in cardiac amyloidosis. Dyer also saw neurologist Dr. Dianna Quan, because sometimes ATTR amyloidosis can manifest in the nervous system.

“It’s this sort of follow-up that really matters to patients,” Crooks says.

“We provide top-quality care because we can take that patient from, ‘Here are your results’ to ‘Here are your options,’” Crooks said – options that include referrals to diverse UCHealth specialists with expertise in these rare, genetically linked diseases.

So it was with Dyer. Other patients’ biobank results arrive before symptoms do, giving patients the opportunity to work with their providers over the long term to learn about their risks, make lifestyle changes to aid in prevention, and to stay up to date about medical options for the best health outcomes, Crooks adds.

In Dyer’s case, imaging studies confirmed amyloid buildup, but also that her disease – which can cause electrical issues in the heart and cardiomyopathy – was still in its early stages. Ambardekar prescribed tafamidis, a drug that delays ATTR amyloidosis disease progression.

“Because we were able to catch this early, she’s going to do quite well long-term,” Ambardekar said. “Sometimes, if people are diagnosed too late in the game, the options are limited.”

Pharmacogenomics results feed into electronic health records

The vast majority of those 22,000 participants with biobank results have had to do with pharmacogenomics. The CCPM team this year added four new genes/gene pairs to the three it already tracked. Those seven genes and gene pairs can impact how the body breaks down or transports dozens of drugs: chemotherapies for cancer treatment, cholesterol-lowering statins, antidepressants, proton-pump inhibitors to treat stomach ulcers, antifungals, antiseizure medications, pain medications, and anti-inflammatory medications among them. In some cases, a drug can be life-threatening to those with a genetic variant that, for example, makes it hard for the body to break it down.

Pharmacogenomic results feed straight into the patient’s electronic health record, and the patient is alerted to the variant as for any other My Health Connection test result.

Christina Aquilante, a CU Skaggs School of Pharmacy professor and the CCPM’s director of pharmacogenomics, says patients who have received biobank results can contact the biobank to connect with a pharmacist to discuss how these results may impact their care. She added that, while automated clinical decision support tools alert doctors and other providers to relevant drug-gene interactions at the point of prescribing, medical professionals can also consult with CCPM pharmacists through a secure chat.

Taken together, Crooks says her 10-person team’s work has led to something “unlike any other biobank in terms of its scale and the patient population we reach.”

One of those patients is certainly grateful.

“I would have been struggling with my primary care doctor trying to figure out why I was so tired, why my heart was racing, why I fainted while I was out walking,” Dyer said. “Now I can pinpoint what my symptoms are and why I’m feeling them. It allows me to rest more – before, I pushed myself pretty hard. But now I give myself space. So it’s perfect for me.”

• Read and sign the biobank consent form in your My Health Connection patient portal.
• The next time your doctor orders a blood draw, an extra blood sample will be conveniently collected for the biobank at no cost to you.

If you have further questions about this study, please call the Biobank at 303.724.9944 or email us at [email protected].

Genetic results are not guaranteed for participants of the biobank. The biobank is primarily a research project to make general discoveries about health and risk of disease using data analysis of large populations. For many people, we will not find any relevant clinical genetic test results to report. Also, not all participant samples will have genetic testing done on them.