After studying the genetic sequences of more than 100,000 people, researchers around the country have started to uncover the root causes of inflammatory bowel disease (IBD), Crohn's disease, and ulcerative colitis. But those studies have a glaring flaw: They are predominantly based on genetic data almost exclusively from individuals of European descent.
Now researchers at the University of Miami Miller School of Medicine are trying to change that. Maria Abreu, M.D., the director of the Miller School's Crohn's and Colitis Center, and Jacob McCauley, Ph.D., director of the Center for Genome Technology and Biorepository Facility, were awarded a $2.9 million grant by the National Institutes of Health (NIH) to spend the next five years collecting and analyzing the genetic data of more than 3,000 Hispanic individuals, to better understand IBD in that community.
Latin Americans have far lower rates of IBD than people in the U.S. or Europe, but Dr. Abreu started seeing Latin Americans quickly developing IBD after moving to the U.S. She wanted to study those changes, but with so few Hispanic gene sequences available to study, Dr. Abreu knew she needed to expand the pool.
Officials at the NIH felt the same, writing in the grant announcement that an "urgent need" exists to increase the diversity of genetic sequencing.
The NIH now recognizes that Hispanic and Black people, who are a very important percentage of our country, are underrepresented in all of these studies."
Dr. Maria Abreu, M.D., Director of the Miller School's Crohn's and Colitis Center
'More Statistical Power in the Numbers'
Drs. Abreu and McCauley have already collected the DNA of nearly 2,000 Hispanic individuals from South Florida. The NIH grant allows them to collect an additional 3,000 more for the IBD study.
Dr. McCauley says that those big numbers are critical. Humans share 99% of their genes, but, he said, "that one percent is a lot." If a study has too few genetic sequences, the differences between them may be random or insignificant. More genetic sequences allow scientists to identify clearer patterns and zero in on specific genes that may contribute to diseases and other ailments.
"There's more statistical power in the numbers," he said. "We've got to change the recruitment and the enrollment process and let these patient populations that haven't really been approached in the past know about these studies, and try to enroll them to help us with these discoveries."
That's a far cry from the days when geneticists purposefully sought out gene sequences from people who came from similar ancestral backgrounds, thinking that such an approach would make it easier to identify changes in their genetic sequences that cause disease. Now, geneticists are scrambling to diversify those gene pools after realizing that a more diverse gene pool actually helps them better understanding the biology of disease.
"A whole slew of genes have been described as increasing the risk of IBD, but they've all been described in Europeans. But what if across different ancestries those same genes are also found? Well, that means that those genes must be very important," Dr. Abreu said. "We'd like to blow up how we're studying these diseases."
Cuban Immigrants See Earlier Onset in Recent Years
Dr. Abreu doesn't want to predict any outcomes, but her colleague Oriana Damas, M.D., found that Hispanic people may be developing IBD after arriving in the U.S. due to the drastic change in their diets, the ever-increasing number of food additives used in the U.S., and other environmental factors that lead to vast changes in their intestinal bacteria.
A study led by Dr. Damas in the Crohn's and Colitis Center found that Cuban immigrants developed IBD an average of seven years after immigration, compared to an average of 30 years to disease several decades ago. The NIH study will allow her to expand those findings to immigrants from Mexico, Central America, South America, and the Caribbean.
"We think the real change that's occurring is diet and intestinal bacteria," she said.
Drs. Abreu and McCauley are working with six other universities that were chosen to participate in the NIH grant as Genetics Research Centers within the Inflammatory Bowel Disease Genetics Consortium (IBDGC) to conduct the study. They expect to start recruiting volunteers to donate blood and saliva samples in early 2023, hoping to attract enough Hispanic individuals with IBD -; and without it -; to have a full range of genetic sequences to study.
For Dr. McCauley, the NIH study represents another step in his ongoing efforts to diversify the gene pool available to scientists. In addition to the work he and Dr. Abreu have already done locally and within the IBDGC, Dr. McCauley is also a founding member of the Alliance for Research in Hispanic Multiple Sclerosis consortium, which seeks to expand the knowledge of another complex disease, multiple sclerosis, in Hispanic communities. He also participates in the NIH's All Of Us Research Program, which is trying to collect a million genetic sequences across the country that researchers can use for large-scale research projects.
McCauley said diversifying the genes available to study is especially important in Miami, since the community is made up of so many immigrants and people from Latin America.
"This is the community we serve in South Florida," he said. "We are one of the most diverse communities in the country. I think that's a lot of value for the research that we do."