Fifteen years ago, when researchers revealed a genetic link between an adverse reaction and one of the most commonly prescribed anticoagulants in the United States, the discovery seemed bound to help anyone in need of the lifesaving blood thinner Warfarin.
The reality, however, was that few of those people would be African American.
“There is a presumption that very significant pharmacogenetic findings in large studies will be robust, but because these are usually discoveries in people of European ancestry, that is not always the case,” says Minoli Perera, pharmacology.
“There’s also this prevailing thought that if research involves only 500 or 600 individuals, the results are always less significant. However studies of minority population tend to be smaller.”
Perera, a faculty member at the Feinberg School of Medicine, is disrupting those notions.
A pioneer in the field of pharmacogenomics — using a patient’s genetic information to predict drug response — for African Americans, Perera is shining a light on the evolutionary differences between populations of African and European ancestry.
“Every time we explore a new angle of pharmacogenomics in minority populations, we reveal novel information about the role genes play in African Americans’ response to drugs,” says Perera. “African Americans come from the oldest population of humans on Earth, meaning they carry with them the most genetic variation.”
Perera’s lab is involved in research on the genomics of drug metabolism and the pharmacogenomics of anticoagulants and inflammatory bowel disease. As first author of a groundbreaking 2013 study published in Lancet, Perera helped usher in a new pharmacogenomics reality for African Americans.
It had been previously determined that polymorphisms, or DNA variations or mutations, in two genes play an especially large role in a person’s response to different dosages of Warfarin, a drug prescribed nearly 23 million times in 2013. Perera’s research helped show that these variations offer far less pharmacogenomic predictive capability in African Americans. Instead, her study revealed how a different polymorphism, specific to African Americans, plays a critical role in how some patients respond to this lifesaving but dangerous drug.
“African Americans carry many population-specific genetic mutations that predispose them to diseases and alter drug response; however, these genetic mutations can only be discovered if we study them,” says Perera.
The recent rapid progression of pharmacogenomics has been bolstered by studies of overwhelmingly European ancestry populations. By exclusively studying minorities, Perera hopes to bridge the pharmacogenomics knowledge gap that exists between black and white populations.
“If we’re to deliver on the promise that precision medicine can allow a physician to prescribe the right drug at the right dose to the right patient, then there has to be a recognition of the inherent differences between populations,” says Perera. “Our lab has discovered several unique and previously unknown genetic biomarkers specific to African Americans with regard to treatment and disease.”
In 2017, Perera published a paper identifying novel genetic variants associated with the risk of venous thromboembolism (VTE) in African Americans. VTE is a potentially deadly clotting disorder and the third most common life-threatening cardiovascular condition in the United States. African Americans are 30 to 60 percent more likely than European Americans to develop the condition.
Because previous genomic research failed to account for population differences, African Americans taking an approved VTE genetic test were nearly always told they didn’t possess the variant associated with increased risk — the tests came back negative because African Americans almost never have the identified polymorphism.
“Only by looking specifically at African American genomes did we reveal a genetic variant that increases the risk of VTE in this population,” says Perera.
Not only is the genetic mutation that Perera discovered specific to blacks it is also common — 37 percent are carriers. The genome-wide association study was completed with 578 African Americans and replicated with an independent cohort of 159 subjects.
“Scientists have a tendency to weigh evidence by its size, but we’re unable to obtain large sample cohorts because genomic information on minority populations simply does not exist in the same way as it does for European Americans,” says Perera. “It can take the participation of seven institutions to get 500 samples, but the findings should not be discounted.”
Perera’s research is now part of a triad of lab priorities that include community engagement and social justice.
A new center, named ACCOuNT — the African American Cardiovascular Pharmacogenomics Consortium — being funded by a five-year, $7.5 million grant from the National Institute on Minority Health and Health Disparities is allowing her to focus on all three.
“If scientists and physicians leave minority populations behind in our push for precision medicine, the health disparities that already exist are compounded,” she says. “Social justice as it pertains to precision medicine is paramount if healthcare is to be equal for all.”
Perera is working on ACCOuNT with investigators from the University of Chicago, the University of Illinois at Chicago, Stanford University, George Washington University, and the Washington DC VA Medical Center. Northwestern collaborators include Clyde Yancy, chief of cardiology and vice dean for diversity and inclusion at the Feinberg School; Kevin O’Leary, chief of hospital medicine; Marc Rosenman, pediatrics; and researchers at the Northwestern University Clinical and Translational Sciences Institute and the Northwestern Medicine Enterprise Data Warehouse.
“Not all of our research is going to make an immediate impact in terms of care, but our study participants are extremely important for future generations,” Perera says. “Identifying population-specific genetic mutations will bring us beyond an era of trial and error and into one of precision medicine for all.”