The DNA of 250,000 people sheds light on the hidden effect of poverty

About a decade ago, many people were confronted with a frightening diagnosis: they had genetic mutations that increased their risk of hypertrophic cardiomyopathy, a thickening of the heart muscles that can lead to sudden death. The good news, says U.S. physician Alexander Bick, is that it was incorrect. Based on genetic data from white patients, the test was wrong. In those people, blacks, the mutations were benign. This Monday, Bick’s team has taken a giant step forward in correcting those errors, publishing at a stroke almost 250,000 complete genomes, the vast majority of which come from groups that have traditionally been ignored in studies of this kind. “This is a unique opportunity to understand how genes affect human health,” he says enthusiastically.

The initiative is part of the All of Us Science Project, a program promoted by the National Institutes of Health in Bethesda, Maryland; the ultimate goal is to read the genomes of over one million Americans. Nearly half of the 250,000 genomes read so far are from “underrepresented racial and ethnic minorities.” In addition, a quarter come from volunteers living below the poverty line. And one in four are from people over the age of 65. Analysis of this unpublished material has already revealed the existence of 275 million unknown genetic variants. “Each of them offers new potential clues to understanding and curing some of the world’s most critical diseases,” says Bick, of Vanderbilt University in Nashville.

The physician cites an example from his laboratory. His team has taken advantage of the project’s immense diversity to find a mutation that protects against chronic kidney disease associated with the APOL1 gene, a phenomenon most commonly observed in people of African ancestry. “The combination of disease-causing and protective mutations is very unusual, found in less than 1 in 200 African Americans. To solve these extremely complicated puzzles, it’s very important to have very large, not just diverse, data sets,” Bick says.

The National Institutes of Health began recruiting volunteers in 2018, striving to increase the diversity of other similar projects, such as the UK Biobank. “We know that DNA is one of many factors that affect health. There are also many social factors, such as poverty. In the past, many of the participants in research studies belonged to the middle class, so it was difficult to study how these social factors interact with genetic factors,” Bick explains. The results of his research were published this Monday in the esteemed scientific journal Nature.

Physician Eliseo Pérez-Stable directs the National Institute on Minority Health and Health Disparities, a Bethesda-based agency that seeks to “improve the health of minority and disadvantaged populations.” Pérez-Stable himself was born in Cuba and, at the age of eight, emigrated with his family to the United States after the Cuban Revolution. The physician stresses the historical lack of diversity in genomic research and affirms that over 90% of the studies have been done with populations of European ancestry.

Drugs that do not work

Pérez-Stable cites the case of clopidogrel, an antiplatelet-aggregating drug used to prevent blood clots in patients who have had a heart attack or stroke or have circulation problems in their arms and legs. “Clopidogrel doesn’t work when a person has a genetic change that affects the processing of the drug. And it turns out that most people of Hawaiian or Pacific Island origin don’t process it, so it doesn’t work as indicated in those populations,” the physician notes. Three years ago, a court ordered pharmaceutical companies Bristol Myers Squibb and Sanofi to pay almost $834 million to the State of Hawaii for marketing clopidogrel there even though it “knew that it was ineffective for many patients,” the Attorney General’s Office says.

The director emphasizes that science has made great discoveries as a result of including diverse populations in genetic analysis. Pérez-Stable himself participated in a 2014 study that identified a specific mutation (6q25) that decreases the risk of breast cancer by 60% and is only found in Latin American women with indigenous ancestry.

The physician recalls another case. The latest drugs to lower bad cholesterol—so-called PCSK9 inhibitors—were discovered thanks to an African American family with very low levels of this substance in the blood. Led by American physician Helen Hobbs, a team of researchers developed drugs to mimic the effect observed in the family.

If we imagine DNA as a sequence of chemical letters with the instructions for a person’s functioning, epigenetic changes would be like accent marks, which can modify the message and trigger illnesses, such as cancer. Perez-Stable emphasizes that living conditions, such as poverty, can provoke epigenetic changes. “There are few studies that have the potential to capture this phenomenon and this project is one of them,” he observes.

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