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Genes play an important role in TB susceptibility
Author: FMHS Marketing & Communications / FGGW Bemarking & Kommunikasie – Sue Segar
Published: 25/03/2024

​New research shows that genetics play a significant role in a person's susceptibility to developing tuberculosis (TB).

Researchers at Stellenbosch University (SU) are part of a scientific consortium investigating genetic susceptibility to TB that found genetics contribute about 26 percent to a person's likelihood of acquiring TB.

The study, conducted by the International Tuberculosis Host Genetics Consortium and led by Dr Haiko Schurz of SU's Division of Molecular Biology and Human Genetics and Dr Vivek Naranbhai affiliated with the University of Oxford, United Kingdom, and numerous other institutions, studied people from different backgrounds to find common genetic factors that affect TB risk globally. The research article, entitled 'Multi-ancestry meta-analysis of host genetic susceptibility to tuberculosis identifies shared genetic architecture', was recently published in the journal eLife.

“We gathered data from 12 studies in nine countries across Europe, Africa and Asia, including over 14 000 people with TB and almost 20 000 who did not have TB," says Prof Marlo Möller of SU's Division of Molecular Biology and Human Genetics, who was also involved in the study. “By studying people from different backgrounds, we hoped to find common genetic factors that affect TB risk globally."

Everyone exposed to Mycobacterium tuberculosis (the bacterium that cause TB) will not become infected with it, and of those who are infected, not all will go on to develop active TB disease.

“Many studies have been done to find out how our genes affect our chances of getting TB. As these studies get bigger or use newer, better ways to look at genes, it is important to put all the data together to see which gene variations are linked to TB risk," explains Möller.

Previous research conducted on small groups of people either found nothing, or results could not be extrapolated to other groups. Pooling data from different studies into a meta-analysis increases the likelihood of finding meaningful results.

“In our study, we combined datasets from different ancestries which allowed us to find our results – that 26,3 percent of the likelihood of getting TB is due to our genes. This holds true for different backgrounds, showing that our genes play a big role in the disease," says Möller.

Scientists have been interested in how genes affect the chances of getting TB for a long time. “More than 100 genes have been studied, but only a few connections have been confirmed in different studies. This might be because the studies did not include enough samples, or they used different methods, or because people in different areas have different genetic backgrounds," explains Möller.

“Additionally, the TB bacterium itself might differ in different places. Before our meta-analysis, there have been 17 studies that looked at genetic variants across the genome in relation to TB susceptibility, only two regions of the genome have shown up in more than one study. One was found in people from Ghana and Gambia, and was also seen in South Africa and Russia. Another genetic region found in Russia was also confirmed in other studies."

According to Möller, the consortium plans to use the dataset further, and have at least two other manuscripts in the pipeline.

“Because TB is complex and the effects of genes are usually small, we need bigger groups of people and different ways to study genetics. Generating genetic data using more appropriate microarrays [tools used for gene analysis] that includes information from a wider range of people, along with better techniques for filling in missing genetic data, can help us gather bigger and more reliable sets of information for future studies.

“Also, using new technologies like long-read sequencing to look closely at specific genes related to TB susceptibility can be helpful. Having more genetic data will let us analyse genetic susceptibility to TB more accurately and explore how different genes work together in fighting off the disease."

Möller says the study demonstrates “how working together and sharing data can help us understand tricky problems and figure out what makes people more likely to get complex diseases like TB."

Caption: Dr Haiko Schurz and Prof Marlo Möller.