Understanding the role genetics play in COVID-19, other diseases

By Todd Neff
UCHealth Today

There’s never been a bad time for a UCHealth patient to donate a sample to the Colorado Center for Personalized Medicine’s biobank. But if you’re curious as to whether you’ve already had COVID-19, there’s never been a better time than right now.

UCHealth and the Colorado Center for Personalized Medicine (CCPM) have worked as a team since the CCPM’s establishment in 2015. UCHealth patients have donated more than 143,000 samples to the CCPM’s biobank of which 30,000 have been genetically analyzed so far. There’s a good reason for that teamwork.

UCHealth is on the front lines of the continuing fight against diseases of all sorts. Genetic variations are increasingly implicated in all sorts of diseases. The CCPM’s mission is to understand the connections between genetics and disease. Such understanding will, its leaders and many others believe, lead to the development of better preventatives and treatments and to help UCHealth and others fight diseases.

Two reasons to contribute to the biobank

COVID-19 is the disease overshadowing all others at the moment. UCHealth offers both coronavirus testing (which tests for the virus itself using a nasal swab) and antibody testing (a blood test that looks for antibodies left behind after the immune system has fought the virus). One can sign up for either test at UCHealth’s My Health Connection portal. If you schedule an antibody blood test, you’ll have the option to allow a second small vial to be filled – a vial which will land at the CCPM’s biobank. There are two good reasons why you might consider doing so.

First, your contribution to the biobank can help advance medical science over the long term. Size matters when it comes to building a genetic database, which is what the CCPM biobank is. While the biobank does retain frozen blood samples, its real power is in its ability to store, classify, and analyze the genetic information derived from the partial sequencing of the DNA in those many blood samples.

Some of these genetic analyses are straightforward: cystic fibrosis, sickle-cell anemia, and Huntington’s disease are all caused by a problem with a single gene of the roughly 25,000 in our genome. But scientists now know that all-too-common maladies such as heart disease, high blood pressure, arthritis, diabetes, cancer, obesity, Alzheimer’s disease, and asthma have strong genetic ties. Crucially, these genetic ties bind not to one, but to dozens, hundreds, or even more genes.

“What we’ve learned over time, particularly with the technology that lets us sequence entire genomes and understand more about genetic variation, is that for many of these complex diseases like asthma, diabetes, and cardiovascular disease, there are literally thousands of genetic variants that are contributing to the risk of those diseases,” said Kathleen Barnes, a University of Colorado School of Medicine geneticist and the CCPM’s director.

To understand such complex connections, one needs a huge number of genetic samples – millions being better than thousands, Barnes says. Some diseases may only occur in one in 100,000 people, after all.
“In genetic research, we really go for big numbers,” Barnes said. “A hundred thousand is just the minimum we think we need to make important discoveries.”

Second, your contribution to the biobank may help you in the near term. While your genetic data is anonymous at the CCPM, its link to your UCHealth medical record number gives you the option of letting CCPM researchers alert your UCHealth doctor as to genetic markers that relate to a growing number of diseases.

“We started by returning pharmacogenetic results – that’s how a patient’s genetic makeup can influence their processing of certain drugs,” said Stephen Wick, a CCPM and CU School of Medicine geneticist and regulatory expert. “Also, we’re going to start looking at cancer and cardiovascular disease, and if somebody has an important genetic marker, we will begin to return those results to patients who wish to have them.”

There’s also a medium-term benefit to be considered, one having directly to do with COVID-19. The CCPM is harnessing its genetic expertise to develop what could become a highly accurate test to determine if someone is currently infected with COVID-19. Today’s tests sample for genetic markers of the SARS-CoV-2 virus that causes the disease. CCPM researchers are harnessing their expertise in a stretch of DNA on chromosome 6 (called the HLA complex) to develop a test to detect the coronavirus based on how the presence of SARS-CoV-2 affects the activation of a patient’s genes in that stretch of DNA.

“We think that by doing this, we’ll be able to capture infections at a much earlier stage of disease, identifying infection in individuals who might be asymptomatic and therefore aren’t being tested,” Barnes said. “We can use those data to also create predictive algorithms to tell us which patients with COVID-19 are most likely to go on to develop worse disease and end up in an intensive care unit.”

Genetics and COVID-19

The CCPM has also been part of the Anschutz Medical Campus’s coronavirus-related mobilization. Wicks and CCPM-geneticist colleague Kristy Crooks led a team of six who developed, tested, and received U.S. Food and Drug Administration certification for a coronavirus RNA test in the span of eight hectic days in March. The CCPM’s testing capability was intended to serve as a backup should front-line testing run into mechanical or other problems, Wicks says.

On a broader scale, the CCPM is part of the COVID-19 Host Genetics Initiative, a consortium of institutions from 45 countries who are generating, sharing, and analyzing data to understand the genetic aspects of COVID-19 susceptibility, severity, and outcomes.
“The purpose of the consortium is for us to all come together with all our genetic tools so that we can try to understand to what extent genetics is contributing to who develops COVID-19 and who doesn’t,” Barnes said.
As part of that effort, the CCPM is sending a consortium-developed survey to all of its 143,000 biobank participants with the aim of associating risk factors and symptoms with genetic data.

Barnes, Wicks and many others at the Colorado Center for Personalized Medicine are grateful to the tens of thousands of UCHealth patients who have helped medical science while potentially helping themselves through their donations to the CCPM biobank. With antibody testing requiring a blood draw regardless, and considering the work the CCPM is doing on the coronavirus and many other diseases, they’re hoping that many, many others join the effort to understand the complex role of genetics in COVID-19 and many other diseases.

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