US Pharm. 2024;49(4):43-46.
Genetics Study Highlights Health Disparities in IBD
The advent of whole genome sequencing technology has prompted an explosion in research into how genetics is associated with disease risk. But the vast majority of genetics research has involved people of European ancestry, and genetics researchers have realized that to address health disparities, more needs to be done.
In a new study, Georgia Tech University researchers investigated whether 25 rare gene variants known to be associated with inflammatory bowel disease (IBD) play a role in risk for African Americans. While the rare variant associations were recently discovered in individuals of European ancestry, contributing to about 15% of cases, it was unknown if and how those same rare gene variants might affect risk for African Americans.
Led by Greg Gibson, regents’ professor and Tom and Marie Patton Chair in the School of Biological Sciences, the study highlights the importance of considering genetic diversity and the mixing of ancestry in genetics research. The findings were published in the journal Genome Medicine.
“Because of major advancements in the last decade, we now know that most diseases are far more complex than we originally thought, in terms of genetics,” said Dr. Gibson, who is also director of the Center for Integrative Genomics at Georgia Tech. “Understanding whether genetic differences contribute to health disparities is a major point of focus for current genetics research, and we had an opportunity to test one idea with this study.”
Today, African Americans have a similar prevalence of various types of IBD as European Americans. But progression is often much worse: African Americans are more likely to progress to severe disease requiring colectomies and other major interventions.
Courtney Astore, a PhD student in Dr. Gibson’s laboratory and first author on the paper, wanted to assess whether those same rare variants would have a similar effect on IBD risk in African Americans. In a collaboration with Subra Kugathasan from Emory University and the National Institutes of Health’s IBD Genetics Consortium, Dr. Gibson’s laboratory had analyzed the complete genome sequences of over 3,000 genomes of African Americans, half with IBD. Ms. Astore used that database to conduct her analysis.
She started by plotting the difference in frequency of the rare variants and quickly realized that there was a significant reduction in prevalence of the variants in African Americans. Through further computations, she estimated that European ancestry variants actually only made a very small contribution to IBD in African Americans (around 44 additional cases per 100,000 people), fourfold less than Americans of European ancestry.
“Prior to our analysis, we suspected that admixture may play a role in the presence of IBD-associated rare variants in African Americans,” Ms. Astore said. “When I saw the differences, that was when I realized that there was something important there that we needed to discover.”
She then used a method known as chromosome painting, which is a tool for visualizing where each segment of the genome comes from, and she showed that the rare variants found in African Americans were almost always located on segments of European ancestry genomes.
In simple terms, the location of the variants indicated that the genes resulted from admixture—mixing of genetic backgrounds throughout ancestry—which enabled Ms. Astore to show that the mutations had arisen outside of Africa and only began to appear in people of African ancestry over the last dozen generations.
To conclude the study, Dr. Gibson and Ms. Astore assessed the presence of other rare variants associated with a dozen other diseases, which similarly confirmed that the presence of the variants contributes to African Americans generally through admixture.
The findings are important for several reasons. First, they highlight the value of considering genetic diversity and admixture in all genetics research, especially when investigating rare variants and their associations with complex disease. While they showed that the European variants were rare in African Americans, there are almost certainly rare variants that contribute to IBD in African Americans that have yet to be discovered and may point to biological mechanisms.
“Doing more genetic studies on diverse populations, and especially those that have admixture, is going to be pivotal for therapeutic discovery,” Ms. Astore said.
Precision medicine will eventually be tailored to a person’s genome, which means that in some cases knowing the identity of rare variants will help guide therapy. If that is the case, knowing the context of ancestry will be beneficial. It also means that if more research on diverse ancestry groups is not done, new treatments might not be effective for all people. The team emphasized that genetics is not the only factor contributing to risk for complex diseases like IBD, and their study simply highlights that it cannot be assumed that genetic discoveries are risk factors for all people.
“Our study emphasizes that in order to move in the direction of greater health equity, it is absolutely crucial to do large-scale genetic sequencing for African Americans and all ancestry groups,” Dr. Gibson said. “We hope our work will encourage more research on both social determinants of health and the genetics of IBD across ancestries.”
More Than Half of American Indian Youth May Have High Cholesterol
More than 70% of American Indian young adults aged 20 to 39 years and 50% of American Indian teens have cholesterol levels or elevated fat in the blood that put them at risk for cardiovascular disease, a study supported by the National Institutes of Health (NIH) suggested. In some cases, these levels, specifically high LDL cholesterol often thought of as “bad” cholesterol, were linked to plaque buildup and cardiovascular events such as heart attack and stroke.
The findings, published in the Journal of the American Heart Association, came from a 19-year review of the Strong Heart Family Study, part of the Strong Heart Study—the largest study of cardiovascular health outcomes and risk factors among American Indian adults. Researchers followed more than 1,400 participants aged 15 to 39 years from 2001 to 2003 and in 2020. At the beginning of the study, 55% of participants aged 15 to 19 years had abnormal cholesterol levels, as did 74% of those aged 20 to 29 years, and 78% of those aged 30 to 39 years.
“We were surprised about the numbers, especially in adolescents,” said Jessica A. Reese, PhD, an epidemiologist in the Center for American Indian Health Research at the University of Oklahoma Health Sciences Center, Oklahoma City. “These findings show the importance of early screenings and interventions, especially for teens and young adults who may be more likely to have underlying cardiovascular risks, diabetes, or chronic liver disease.”
The researchers defined patients’ cholesterol as abnormal if they had either high total cholesterol; high LDL cholesterol or other types of “bad” cholesterol; moderately high triglycerides; low HDL cholesterol, often thought of as “good” cholesterol; or if they had been prescribed cholesterol-lowering medication.
About 40% of study participants had high LDL levels (at least 100 mg/dL), while nearly 3% had very high levels (at least 160 mg/dL). However, less than 2% of participants with very high LDL cholesterol took cholesterol-lowering medication at the start of the study.
“This research supports efforts to identify ways, such as increased screenings and culturally relevant education, to improve heart health and support younger generations of Native Americans,” said Mona Puggal, MPH, an epidemiologist in the Division of Cardiovascular Sciences at the National Heart, Lung, and Blood Institute, part of NIH.
Heart disease is twice as high in American Indian adults compared with the general U.S. population. Abnormal cholesterol levels seen among participants in the current study were also twice as high as abnormal levels seen in the general population of U.S. teens and young adults. Researchers underscored the value of routine check-ins and screenings. All participants in this observational study were also notified about their laboratory work and imaging results after their physical examination, and researchers encouraged them to take the results to their healthcare providers.
At the start of the study, 1,165 participants had ultrasounds of the carotid artery, an artery in the neck that carries blood from the heart to the brain. Approximately 61 (5%) showed signs of plaque or early plaque development. Plaque can prohibit blood flow to the heart or rupture when too much of it accumulates in an artery, and that can lead to a stroke or need for surgery.
About 5.5 years after the baseline measurements, 19 participants—about one-third of those with detectable plaque—had signs of their plaque getting worse. Among the 1,104 who did not have detectable plaque at the beginning, 109 (10%) had signs of it during the second check-in. Researchers linked high levels of LDL cholesterol, total cholesterol, and other non-HDL cholesterol to these outcomes.
By the end of the study, approximately 127 participants (9%) had experienced a heart attack, stroke, heart failure, or a related heart surgery or death. Participants who had diabetes and at least a few cardiovascular risks, such as having a large waistline, high blood sugar, high triglycerides, high blood pressure, or low levels of HDL cholesterol, were also more likely to have cardiovascular events.
To support early risk detection, researchers emphasized the importance of youth staying connected to healthcare providers.
Does Failure to Understand Race Lead to Flawed Health Technology?
A study that focused on wearable health monitors underscores an entrenched problem in the development of new health technologies—namely, that a failure to understand race means the way these devices are developed and tested can exacerbate existing racial health inequities.
“This is a case study that focuses on one specific health monitoring technology, but it really highlights the fact that racial bias is baked into the design of many of these technologies,” said Vanessa Volpe, coauthor of the study and an associate professor of psychology at North Carolina State University.
“The way that we understand race, and the way that we put that understanding into action when developing and using health technologies, is deeply flawed,” said Beza Merid, corresponding author of the study and an assistant professor of science, technology, innovation, and racial justice at Arizona State University.
“Basically, the design of health technologies that purport to provide equitable solutions to racial health disparities often define race as a biological trait, when it’s actually a social construct,” Dr. Merid said. “And the end result of this misunderstanding is that we have health technologies that contribute to health inequities rather than reducing them.”
To explore issues related to the way the development and testing of health technology can reinforce racism, the researchers focused specifically on photoplethysmographic (PPG) sensors, which are widely used in consumer devices such as Fitbits and Apple watches. PPG sensors are used in wearable technologies to measure biological signals, such as heart rate, by sending a signal of light through the skin and collecting data from the way in which the light is reflected back to the device.
For the study, the researchers drew on data from clinical validation studies for a wearable health monitoring device that relied on PPG sensors. The researchers also used data from studies that investigated the ways in which skin tone affects the accuracy of PPG “green light” sensors in the context of health monitoring. Finally, the researchers looked at wearable device specifications and user manuals and data from a lawsuit filed against a health technology manufacturer related to the accuracy of technologies that relied on PPG sensors.
“These studies identified challenges with PPG sensors for people with darker skin tones,” said Dr. Merid. “We drew on scholarship exploring how innovative technologies can reproduce racial health inequities to dig more deeply into how and why these challenges exist. Our own expertise in responsible innovation and structural racism in technology guided our approach. If people are developing technologies with the goal of reducing harm to people’s health, how and why do these technologies end up with flaws that can exacerbate that harm?”
The findings suggest that there are significant challenges when it comes to “race correction” in health technologies. Race correction is a broad term that not only applies to technologies but also involves correcting or adjusting health risk scores that are used to make decisions about the relative risk of disease and the allocation of healthcare resources.
“Race correction assumes that we can develop technologies or health risk scoring algorithms to first quantify and then ‘remove’ the effect of biological race from the equation,” said Dr. Merid. “But doing so assumes race is a biological difference that needs to be corrected for to achieve equitable health for all. This prevents us from treating the real thing that needs to be corrected—the system of racism itself (e.g., differential treatment and access to healthcare, systematic socioeconomic disenfranchisement).”
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