Genetic Diversity in Tanzanian TB Patients

Africa has the greatest genetic diversity among humans. This diversity comes from many different ethnic and language groups living on the continent. The long history of human evolution in Africa and the large populations have led to this variety. In recent years, migration and mixing between these groups have also played a role, leading to some similarities among them. Today's African populations often have a mix of different ancestries.

One significant migration event that changed the population in Africa is known as the 'Bantu expansion.' Bantu-speaking people moved from Central Africa to the south and east, bringing farming methods and mixing with local hunter-gatherers and pastoralists. Studies show there are still some noticeable differences among Bantu-speaking groups, but mixing with local populations has affected how they respond to diseases.

Diseases, especially infectious ones, have been major factors in human evolution. Because of this, how people react to diseases can vary widely among different populations. Recent genetic studies have pointed out specific mutations that can change how likely someone is to contract certain infectious diseases, like tuberculosis (TB), which is still the leading cause of death from a single infectious agent.

The bacteria responsible for TB belong to a group called the Mycobacterium tuberculosis complex (MTBC), which has ten lineages adapted to infect humans, and various other lineages that infect animals. While TB is a global issue, the lineages that affect humans are found in different parts of the world. Some lineages are very common worldwide, while others are limited to specific regions. For instance, some lineages are mostly found around the Indian Ocean or are primarily seen in certain areas of Africa.

The relationship between the bacteria that cause TB and the human populations they infect is complex. Research shows that the strains of TB can be closely linked to the geographical background of the patients. This connection can be broken in people who are also infected with HIV. Different strains of the bacteria also have different characteristics, affecting how the disease progresses, how it spreads, and how it shows up in patients.

Variability in how people respond to TB can also be traced back to their genetic backgrounds. Certain genes in different populations can make them more susceptible to TB, and specific groups have shown different levels of risk for developing the disease. Alongside this genetic diversity, many factors like malnutrition, HIV, diabetes, poverty, smoking, and alcohol use also play important roles in the spread and severity of TB.

Though there have been many studies on how individual factors relate to TB, there haven't been many that look at all these elements together.

In this study, we looked at the genetic backgrounds of TB patients in Dar es Salaam, Tanzania. We aimed to understand the genetic ancestry of these patients, to identify the TB bacteria affecting them, and to see how both of these factors relate to the severity of their diseases.

#Genetic Ancestry of Tanzanian TB Patients

We estimated genetic ancestries for 7,479 individuals from 249 populations, which included 1,444 Tanzanian TB patients. We used data from 53,255 SNPs (single nucleotide polymorphisms). The analysis revealed three main genetic ancestries among the Tanzanian TB patients.

The most significant genetic ancestry was called “Southeastern Bantu,” which contributed an average of 44%. This ancestry is also prevalent among other Bantu-speaking groups in Southern and Southeastern Africa. The next most common ancestry was “Eastern Bantu,” making up about 22%. This ancestry is common in Kenyan populations. There was also a “Western Bantu” ancestry found in Tanzanian patients, averaging 9%, which is more common among Bantu groups from Western Central Africa.

Other less common ancestries present included minor contributions from Nigerian populations, populations from Chad and Sudan, and hunter-gatherer groups from Western Africa. Overall, Tanzanian TB patients showed little non-African ancestry, averaging around 5%, with very few patients having over 30% non-African ancestry.

This genetic analysis indicated that the majority of TB patients in Tanzania were primarily of Bantu descent, reflecting a mixture of different Bantu components.

#Insights Into Bantu Genetic Ancestries

By combining data from many Bantu groups, we saw that populations in Kenya and Mozambique also displayed significant portions of Bantu ancestry, showing how these ancestries spread across the region. The Eastern Bantu ancestry was highest in Kenya and Tanzania but decreased farther south and west. In contrast, the Southeastern Bantu ancestry increased towards the south and decreased towards the west.

The Western Bantu ancestry was most prevalent in populations from Gabon, Cameroon, and South Africa. A clear correlation was found between the geographical distribution of human populations and their genetic distances.

Even though our TB patients were all from Dar es Salaam, they belonged to a variety of ethnic groups from different regions within Tanzania. This geographic diversity was linked to genetic differences among the patients, reinforcing the idea that human genetic diversity in Tanzania is structured by geography.

We found that for Tanzanian TB patients, the Southeastern Bantu ancestry increased from the west to the east, while the Eastern Bantu ancestry showed the opposite trend. The Western Bantu genetic ancestry increased towards the north and decreased towards the east.

#MTBC Genotypes in Tanzania

We previously found a wide variety of MTBC genotypes in Tanzanian TB patients, with four main genotypes being responsible for a significant number of cases. These dominant strains had been introduced into Tanzania over 300 years ago. The most prevalent genotype (L3.1.1) accounted for around 39% of TB cases.

Despite the presence of these dominant strains, we did not find any significant relationships between the different MTBC genotypes and the severity of TB diseases in patients. We used measures like X-ray scores, bacterial load, and clinical scores to assess disease severity but found no correlation.

#Relationship Between Human and Bacterial Genotypes

We also looked into whether there might be any host genetic factors affecting how the different MTBC genotypes behaved. When comparing the genetic backgrounds of patients infected with different strains, we found minor differences in their genetic ancestry proportions. There were no significant correlations between the human genetic distances and those of the bacteria.

These findings suggest that the transmission and duration of infectious periods were more likely influenced by the bacterial genotypes rather than the genetic ancestry of the human hosts.

#Human Genetic Ancestry and TB Disease Severity

Next, we checked if the genetic ancestry of the TB patients influenced disease severity. We conducted logistic regression analyses considering three different proxies for TB severity while controlling for factors like age, sex, HIV status, and other health conditions.

Despite our expectations, we found no evidence linking human genetic ancestry to the severity of TB disease among the patients we studied.

#Combined Effect of Human and MTBC Genetic Diversity

For a smaller group of 1,000 TB patients, we had both human and bacterial genetic data available. While previous research has indicated that genetic interactions between humans and bacteria can impact TB severity, we did not find support for this in our analysis.

When we added the dominant MTBC genotype into our models, along with its interaction with human ancestry, no significant effects on TB severity were observed.

#Conclusion

Our study indicates that TB patients from Dar es Salaam have mostly Bantu genetic ancestry with minimal Eurasian genetic influence. We found no evidence that the genetic backgrounds of the patients or the MTBC strains significantly impacted TB disease severity, suggesting that other factors like social conditions and environment play a more crucial role in Tanzania’s TB situation.

The results show that, despite the genetic diversity present in Tanzania, the TB patient population we studied primarily reflects recent migrations and does not capture the full array of human genetic diversity on the continent. The underlying MTBC strains, however, indicate that they have been influenced by multiple historical introductions and have adapted successfully to the local population over time.

This understanding emphasizes the importance of considering both human and bacterial genetics in public health efforts and highlights the need to address the social and environmental factors driving TB transmission and severity in regions like Tanzania.