FEB 23, 2021 7:34 AM PST

New Insight Into Genetic Basis of IBD From African-American Patients

WRITTEN BY: Carmen Leitch

The small variations in the genome that lead to differences in biology, including risk for diseases, can't be assumed to be the same for different populations, new work has shown. Genome-wide association studies should include people with varied ancestry. For example, the genetic risk factors that affect the development of inflammatory bowel disease (IBD) in African Americans are not the same as those in people of European ancestry.

Image credit: Pixabay

Reporting in the American Journal of Human Genetics, researchers looked at the whole genome sequences from 1,700 Crohn's disease and ulcerative colitis patients and around 1,600 unaffected individuals. The work showed that IBD studies should account for ancestry.

"Even though the disease destination looks the same, the populations look very different, in terms of what specific genes contribute to risk for IBD," said lead study author Subra Kugathasan, M.D., the Marcus professor of pediatrics and human genetics at Emory University School of Medicine among other appointments. "It shows that you can't develop a polygenic risk score based on one population and apply it to another."

Polygenic risk scores are used to describe how likely a person is to develop a complex disease like heart disease based on their genes. As we learn more about the genome, they become more useful.

The biggest risk factor for IBD is having a first-degree relative with a form of IBD, moreso than any environmental factor. This research suggested that for African Americans, the more significant risk locus is PTGER4, a minor one in European populations, noted Kugathasan. But the two primary European gene loci, NOD2 and IL23R, have smaller roles in African Americans. There is overlap in some genetic risk factors, such as IL23R, because there is some European ancestry in the African-American genetic background.

"One of our goals in treating IBD is to move toward a more personalized approach," said Dermot McGovern, M.D., Ph.D., the Joshua L. and Lisa Z. Greer Chair in Inflammatory Bowel Disease Genetics at Cedars-Sinai. "Deciphering the genetic architecture is an important part of this effort. Studies such as this one are vital to ensure that diverse populations, including African-Americans, benefit from the tremendous advances promised by genomic medicine."

Kugathasan noted that there is a therapy being developed for IBD that targets the IL23 receptor pathway, in part because of the risk factor; as such, work on PTGER4 should expand.

This work also revealed some rare genetic variants that are associated with IBD and have not been found in other populations. These variants were linked to a gene involved in nervous system signaling, CALB2.

The researchers were disappointed that they did not discover more variants that can adequately explain IBD risk in African-Americans that is likely to come from the genome, but is not explained by known variants.

Additional research investigating how IBD may be affected by the interaction between genes and environmental factors like diet, toxins, or the microbiome will be needed and may reveal more, suggested Kugathasan.

Sources: AAAS/Eurekalert! via Emory Health Sciences, American Journal of Human Genetics

About the Author
BS
Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
AUG 30, 2022
Cell & Molecular Biology
Rare Genetic Condition Discovered in Ancient Human
AUG 30, 2022
Rare Genetic Condition Discovered in Ancient Human
While most of us are born with 2 sex chromosomes in either a combination of XX or XY, there are many cases of people who ...
SEP 12, 2022
Genetics & Genomics
Deciphering Longevity with the Genetics of the Immortal Jellyfish
SEP 12, 2022
Deciphering Longevity with the Genetics of the Immortal Jellyfish
Living things have to contend with aging. Except for a few unusual creatures, like Turritopsis dohrnii, which has an ext ...
SEP 16, 2022
Coronavirus
Persistent COVID Cases Seem to Encourage Viral Mutations
SEP 16, 2022
Persistent COVID Cases Seem to Encourage Viral Mutations
The majority of SARS-CoV-2 infections start to get better within several days, although infected people can shed virus a ...
OCT 05, 2022
Cell & Molecular Biology
Researchers Discover Muscle Disease Starts Earlier Than Thought
OCT 05, 2022
Researchers Discover Muscle Disease Starts Earlier Than Thought
People with Duchenne muscular dystrophy (DMD) start to experience symptoms in early childhood. The disease is caused by ...
NOV 04, 2022
Immunology
From Fleas to Natural Selection: The Black Plague & Modern Immunology
NOV 04, 2022
From Fleas to Natural Selection: The Black Plague & Modern Immunology
Acknowledgments of our many physiological changes since the evolution of modern humans have been studied profusely, espe ...
NOV 29, 2022
Drug Discovery & Development
Chemotherapy May Increase Disease Susceptibility for Two Generations
NOV 29, 2022
Chemotherapy May Increase Disease Susceptibility for Two Generations
A common chemotherapy drug may make future generations more susceptible to disease. The corresponding study was publishe ...
Loading Comments...