Closing the genomics gap: How to improve indigenous health

Experts are gradually gaining insight into genetic variations in Latin America, Africa, and Asia, with the aim of expanding and refining medical therapies.

Seemingly tiny genetic variations hold the secrets to why many of us contract illnesses, like cancer, and how we react to treatments for them.

The sequence of genes, or biological data, that allows us to function and sustain life. However, the 0.1% of human DNA that varies among each of us can reveal the factors responsible for diverse health outcomes.

What I'd like to explore with you is whether certain lifestyle factors can influence our likelihood of developing diseases.

A primary concern in genetics is that over 80% of research involves individuals of European ancestry, failing to represent more than 20% of the global population. Consequently, this is leading some experts to argue that such studies may perpetrate an injustice in the field of medicine.

"We are aware of the genetic basis of diseases much more for individuals of European ancestry, including those from the US, compared to people from other parts of the world," said Eduardo Tarazona-Santos, a geneticist at Universidade Federal de Minas Gerais in Brazil.

Tarazona-Santos has been working to rectify this injustice, gathering data on genetic disparities in two indigenous populations in Latin America — one located in the Andean highlands and the other in the Amazonian lowlands.

The study discovered that minute genetic differences resulted in diverse reactions to medications used to prevent blood clots and treat high cholesterol.

Despite living only 20 to 40 miles apart, the genetic differences between the groups were as significant as those seen between Europeans and East Asians.

"Our research highlights the importance of recognizing that communities commonly perceived as being of a single ethnic group, such as indigenous peoples in the Americas, are actually much more diverse than often assumed," Tarazona-Santos told Weden News.

Understanding the genetic differences between indigenous groups can have significant implications for our understanding of human evolution, disease susceptibility, and the impact of genetic factors on health and development. It can also inform conservation efforts, cultural heritage preservation, and the development of personalized medicine.

Tarazona-Santos' team analyzed genetic data from 249 individuals in 17 ethnic groups. "We then checked the prevalence of genetic variants that influence how people respond to medicines," said study co-author Victor Borda.

Researchers discovered disparities in two particular genes - one called ABCG2 and the other VKORC1 - between the high-altitude Andean highlanders and the Amazonians living at lower elevations.

"These genetic variants are crucial as the ABCG2 variant affects the efficacy of simvastatin, commonly prescribed for lowering cholesterol levels. Individuals with the undesirable combination of variants will likely benefit from an alternative medication," Borda explained.

They discovered that 2% of Andeans require a substitute treatment for simvastatin, whereas 14% of the Amazonian population would need an alternative.

The results also indicated that alterations in the VKORC1 gene can affect reactions to the medication warfarin, which is administered to prevent blood clots and lower the likelihood of heart attack and stroke.

"We determined that 69% of the Andean population and 93% of the Amazonian population would benefit from a lower warfarin dosage, primarily as a result of their presence of the VKORC1 genetic variant," said Tarazona-Santos.

Dr. Segun Fatumo, a geneticist at Queen Mary University of London, UK, indicated that the study demonstrated the significance of geneticists analyzing diverse population groups.

"There are many other populations like the Andean and Amazonian indigenous people worldwide that need to be studied in a similar manner," said Fatumo.

Precision medicine could help indigenous communities develop tailored treatments for rare diseases, which are prevalent in some of these groups. "Although indigenous peoples generally have a shorter life expectancy and a higher infant mortality rate than other populations, this need is also brought home by a sobering statistic - infant mortality ranges from 19 to 44 deaths per 1000 live births with no indigenous community having a rate of less than 25 deaths per 1000 live births."

Precision medicine is a treatment system that uses a person's unique health information, including their genetic profile, to create treatments tailored to their personal health needs - as opposed to the traditional "one-size-fits-all" approach.

"It can help us provide more tailored treatments to individuals based on their genetic profiles, as studies like this one illustrate with drugs such as warfarin," said Fatumo.

So far, precision medicine using genetic data has greatly benefited individuals of European descent significantly. Tarazona hopes that these new research findings will extend precision medicine to indigenous populations who are part of the Brazilian healthcare system.

Dr. Tarazona-Santos stated that this could lead to an improvement in the treatment for children with leukemia and could also prevent adverse reactions to certain medications, including antidepressants and some cardiovascular disease treatments.

Single-focus genomic analysis is detrimental to scientific progress.

Fatumo stated science has "done self-harm" by not expanding genomics research more quickly: "There are so many more similar genetic variations to be discovered in other populations. They can aid in finding new treatments and understanding why some drugs are more damaging or beneficial to certain individuals, but not others."

In Africa and Asia, as well as in Latin America, significant portions of large programs, including The Nigerian 100K Genome Project.

Researchers from Tarazona-Santos' team are now working on a much larger data set, sequencing 60,000 Brazilian genomes from various ancestral backgrounds.

Groundbreaking global genetics research is producing remarkable results. "We have treatments that reduce cholesterol levels and prevent heart attacks. PCSK9 inhibitors were discovered because individuals with African ancestry had genetic mutations in the PCSK9 gene, leading to lower cholesterol levels," Fatumo explained to Weden News, pointing out that there are likely to be numerous similar treatments found by studying genetic data from diverse populations around the world.

Edited by: Zulfikar Abbany

Primary source:

http://dx.doi.org/10.1016/j.cell.2024.07.009

Author: Fred Schwaller