Georgia Tech Study Investigates IBD Genetic Variants in African Americans

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Left: Chromosome painting for an African American control carrying four inferred causal Sazonovs et al. variants. Right: Chromosome painting for an African American IBD case carrying four inferred causal Sazonovs et al. variants. The blue and pink colors in the chromosome paintings represent African and European, respectively. (Image Credit: Georgia Institute of Technology)

Georgia Tech researchers have recently conducted a significant study focusing on the association between genetics and inflammatory bowel disease (IBD) in African Americans. The study, led by Greg Gibson, Regents’ Professor, and Tom and Marie Patton Chair in the School of Biological Sciences, and published in Genome Medicine, investigates the role of 25 rare gene variants in IBD risk among African Americans. These variants were previously identified in individuals of European ancestry, contributing to about 15% of IBD cases, but their impact on African Americans was unclear.

The Significance of Genetic Diversity in Research
The study underscores the necessity of considering genetic diversity and the mixing of ancestry in genetics research. "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," stated Gibson. The research team's approach involved analyzing the complete genome sequences of over 3,000 genomes of African Americans, half of whom have IBD. This analysis was conducted in collaboration with Subra Kugathasan from Emory University and the NIH’s IBD Genetics Consortium.

Courtney Astore, a Ph.D. student in Gibson’s lab and first author of the paper, performed the analysis using the extensive database. She observed a significant reduction in the prevalence of the variants in African Americans. Further computations suggested that these variants contributed to IBD in African Americans far less than in Americans of European ancestry.

Innovative Methods in Identifying Genetic Variants
Astore employed a technique known as chromosome painting to visualize the origin of each genome segment. This analysis revealed that the rare variants in African Americans were primarily located on segments of European ancestry. This finding indicates that these gene mutations, linked to IBD, originated outside of Africa and appeared in African populations over the last several generations.

Implications for Future Research and Precision Medicine
The research highlights the importance of conducting genetic studies in diverse populations, particularly those with mixed ancestry, for the advancement of therapeutic discovery. Astore emphasized the role of such studies in precision medicine, where treatments are tailored to an individual's genome. Understanding the context of ancestry is vital in this regard.

Furthermore, the study stresses that genetic factors are not the sole contributors to complex diseases like IBD. It calls for comprehensive research on both social determinants of health and genetics across various ancestries. "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," Gibson concluded. This research is a step towards addressing health disparities and enhancing our understanding of the genetics underlying IBD in different populations.