Closing the genomics gap: How to improve indigenous health

Nestled amongst subtle genetic differences are clues for why many of us develop diseases, like cancer, and how we respond to medical treatments for them.

We share 99.9% of human DNA — the sequence of genes, or biological information, that allows us to function and live. But the 0.1% of human DNA that differs in each of us can reveal why we have different health outcomes.

There's a lot of research into genetics and genomics as these fields can explain how genes are passed from generation to generation, and how all of our genes together — our genomes — make us more or less likely to develop a disease. 

The problem is that more than 80% of genetics studies include only people from European descent. As a result, they represent no more than 20% of the worldwide population. And that is leading to what some experts an injustice in medicine — or a "genomics gap".

"There is an injustice in medicine, particularly in genetics: we know much more about the genetic basis of diseases for people of European ancestry [Europeans or US-whites] than for people with other origins," said Eduardo Tarazona-Santos, a geneticist at Universidade Federal de Minas Gerais in Brazil.

Tarazona-Santos has been working to fix this injustice, gathering data about genetic differences in two indigenous populations in Latin America — one in the Andean highlands and the another in the Amazonian lowlands.

Published in the journal Cell, the study found that subtle genetic differences caused varying responses to medications that treat blood clots and high cholesterol.

The genetic differences were as large as those observed between Europeans and East Asians, despite the two groups living only 100 to 200km (60 to 125 miles) apart.

"Our findings emphasize the need to consider that ethnic groups that frequently are considered as homogeneous, such as indigenous peoples of the Americas, are actually not homogeneous," Tarazona-Santos told DW.

Genetic differences between indigenous groups

Tarazona-Santos' team analyzed genetic data from 249 individuals from 17 indigenous traditional populations. "We then checked the prevalence of genetic variants that affect response to drugs," said study co-author Victor Borda.

They found differences in two specific genes — one called ABCG2 and the other VKORC1 — between the Andean highlanders and the Amazonians lowlanders.

"These genetic variants are important because the ABCG2 variant influences the therapeutic success of simvastatin, used to treat high cholesterol levels. Those individuals with the 'wrong' combination of variants should use a different drug," said Borda.

But they found that only 2% of Andeans would need an alternative treatment to simvastatin, whereas 14% of Amazonians would need an alternative.

The results also showed that variants in the gene VKORC1 could influence responses to the drug warfarin, which is used to treat blood clots and reduce the risk of heart attack and stroke.

"We found that 69% of the Andean versus 93% of the Amazonian people would require a lower dosage of warfarin, due to [their having] the VKORC1 genetic variant," said Tarazona-Santos.

Segun Fatumo, a geneticist at Queen Mary University of London, UK, said the study exemplified why geneticists need to analyze other diverse populations.

"There are so many other populations like [the Andean and Amazonian indigenous people] around the world that need to be studied in the same way," said Fatumo.

Precision medicine could help indigenous communities

Precision medicine uses a person's specific health data, including their genetics, to tailor medical treatments to their individual needs — rather than a conventional "one-size-fits-all" approach.

"It can help us to give much more appropriate treatments to someone based on their genetics, like this study shows with drugs like warfarin," said Fatumo.

But so far, precision medicine using genetic data has overwhelmingly helped people from European descent. Tarazona hopes the new research will bring precision medicine to people from indigenous backgrounds who are in the Brazilian health system.

Tarazona-Santos said this could improve treatment for children with leukemia and avoid adverse drug responses, or treatments with antidepressant drugs and some cardiovascular diseases.

Non-diverse genomic studies are 'self-harm' in science

Fatumo said science had done "self-harm" by not diversify genomics research faster: "There are so many more similar genetic variants to be found in other populations. They can help find new treatments, and [let us] understand why some drugs are more harmful or beneficial to certain people but not others."

But things are changing. There are genetic analyses underway in Africa and Asia, as well as Latin America, often part of big programs, such as The Nigerian 100K Genome Project.

And Tarazona-Santos' group has started work on a much bigger data set, sequencing 60,000 Brazilian genomes from different origins.

New global genetics research is beginning to bear fruit. "We have treatments that lower cholesterol and prevent heart attack. PCSK9 inhibitors were discovered because some African ancestry individuals had genetic variants in the PCSK9 gene that caused them to have lower cholesterol," Fatumo told DW, adding that there were likely to be many more similar treatments to be found by studying the gnomes of people around the world.

Edited by: Zulfikar Abbany

Primary source:

The need to diversify genomic studies: Insights from Andean highlanders and Amazonians published by Alvim et al. in the journal Cell (August 2024) http://dx.doi.org/10.1016/j.cell.2024.07.009