Crohn's disease and ulcerative colitis are chronic autoimmune
diseases that affect as many as 1.4 million Americans. Patients with
these inflammatory bowel diseases (IBD) have immune systems that attack
their own intestines, resulting in inflammation.
Although historically a
disease of the developed world and populations of European ancestry,
recent years have seen a steady increase in reported cases of IBD in
‘Two regions of the genome (loci) associated with ulcerative colitis only in people of African descent have been identified by researchers.’
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
In more than 1,000 studies of IBD genetics in white and Asian
populations, more than 200 susceptibility loci for IBD have been
identified in populations of predominantly European ancestry, and at
least 35 loci have been identified in Asians, with a few that appear to
The research team hypothesized that a high-density GWAS of IBD in
African-Americans could identify population-specific variants, further
define IBD genetic architecture, and expose novel disease mechanisms.
"Although most human gene mapping has been done in people of
European background, inflammatory bowel disease is not race-specific,"
says Subra Kugathasan, professor of pediatrics at Emory University
School of Medicine and corresponding author of the study. "Genome-wide
studies lag behind in non-European populations, and African-Americans
are the last group not to be studied specifically. As new therapies are
developed, it will be important to know the genotype of individuals we
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 IBD (1,646 with Crohn's disease, 583
with ulcerative colitis, 116 with unclassified IBD), and 5,002
individuals without IBD (controls).
The study identified single-nucleotide polymorphisms (SNPs) - at
ZNF649 and at LSAMP - with genome-wide significance in ulcerative
colitis. These SNPs 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 IBD, and these loci will be added to the already known
200+ loci in IBD to further expand the IBD genetic architecture. The
team also found evidence of overlapping genome-wide associations for
ulcerative colitis and IBD 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 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 IBD."
The study's first author was Steven Brant, 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 IBD risk in only people
of African descent demonstrates the importance of studying the genetics
of IBD 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 IBD - 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 IBD 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 GWAS of AA IBD 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 IBD 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 IBD in AAs. Such research is paramount to allow
for the future benefits of IBD genetics research, from risk prediction
and family counseling to targeted therapies and eventually disease
preventive strategies to be available for the under-studied AA