In the first genome-wide association study (GWAS) of genetic risk factors for inflammatory bowel disease in African Americans, a research team has identified two regions of the genome (loci) associated with ulcerative colitis only in people of African descent. The study was led by Emory University, the Johns Hopkins University School of Medicine, and Cedars-Sinai and is published online in the journal Gastroenterology.
The research team hypothesized that a high-density genome-wide association study of inflammatory bowel disease in African-Americans could identify population-specific variants, further define inflammatory bowel disease genetic architecture, and expose novel disease mechanisms.
In the current study, conducted at 35 institutions in the United States and Canada, researchers used the genome-wide association study (GWAS) chip to perform high-density, genome-wide scans including 2,345 cases of African Americans with inflammatory bowel disease (1,646 with Crohn’s disease, 583 with ulcerative colitis, 116 with unclassified IBD), and 5,002 individuals without inflammatory bowel disease (controls).
The study identified single-nucleotide polymorphisms (SNPs) at ZNF649 and at LSAMP with genome-wide significance in ulcerative colitis. These single-nucleotide polymorphisms are very specific to sub-Saharan Africans and are not found in any other populations – making these findings unique and novel. This is the first time African- specific loci are known to contribute to inflammatory bowel disease, and these loci will be added to the already known 200+ loci in inflammatory bowel disease to further expand the inflammatory bowel disease genetic architecture. The team also found evidence of overlapping genome-wide associations for ulcerative colitis and inflammatory bowel disease in African- Americans and other populations.
“The hope for genetic advances is that we will be able to develop new therapies and more personalized approaches to managing these chronic and potentially debilitating diseases,” says Dermot McGovern, MD, PhD of Cedars-Sinai and co-senior author with Kugathasan and Brant. “These benefits should be available to all sections of society. This study is important, as it extends these possible advances to the African-American population, who may be at risk of more severe inflammatory bowel disease.”
The study’s first author was Steven Brant, MD, director of the Johns Hopkins Meyerhoff Inflammatory Bowel Disease Center. In addition to Brant, Kugathasan and McGovern, the study was authored by 40 other physicians and researchers in the United States and Canada.
“The detection of variants associated with inflammatory bowel disease risk in only people of African descent demonstrates the importance of studying the genetics of inflammatory bowel disease and other complex diseases in populations beyond those of European ancestry,” say the authors.
In a previous study using the Immunochip genotyping platform, and also published in Gastroenterology, the research team had evaluated more than 1,500 African-American patients with inflammatory bowel disease — including 1,088 with Crohn’s disease and 361 with ulcerative colitis — from 35 IBD centers across North America and used 1,797 African-Americans without inflammatory bowel disease for comparison. They found that gene variants within three of the most highly associated regions for Crohn’s disease in whites — NOD2, interleukin 23 receptor (IL23R) and a region on chromosome 5 known as 5p15.1 — are also important risk factors for Crohn’s disease in African-Americans.
The authors summarize: “This first genome-wide association study of AA inflammatory bowel disease has demonstrated unique, African specific loci, as well as loci that are shared across multiple populations. While some of these shared loci contain unique association patterns and African specific risk variants, many contain universal risk variants (like HLA-DRB1) or risk variants that have arisen from European admixture (like NOD2).
“Given our results and the evolution of inflammatory bowel disease genetics research in non-European populations, it is clear that further studies with larger sample sizes in the AA population are needed to identify additional population specific variants and novel loci, as well as more fully characterize the role of risk variants established in other populations on the development of inflammatory bowel disease in AAs. Such research is paramount to allow for the future benefits of inflammatory bowel disease genetics research, from risk prediction and family counseling to targeted therapies and eventually disease preventive strategies to be available for the under-studied AA population.”
Publication: Genome-wide Association Study Identifies African-Specific Susceptibility Loci in African Americans with Inflammatory Bowel Disease.
Adapted from press release by Emory Health Sciences