The DNA of 250,000 people illuminates the most hidden effect of poverty

About a decade ago, scores of people were faced with a frightening diagnosis: They had genetic mutations that increased their risk of hypertrophic cardiomyopathy, a thickening of the heart muscles that can cause sudden death.

The good news, says American doctor Alexander Bick, is that it was a lie.

The test, based on genetic data from white patients, was wrong.

In those black people, the mutations were benign.

Bick's team takes a giant leap this Monday to correct these errors and publishes almost 250,000 complete genomes at once, the vast majority coming from groups traditionally ignored in this type of studies.

“It is a unique opportunity to understand how genes affect human health,” he celebrates.

The initiative is part of the scientific project All of us, a program promoted by the National Institutes of Health, in Bethesda (USA), with the ultimate goal of reading the genomes of more than one million Americans.

Nearly half of the 250,000 genomes read so far are from “underrepresented racial and ethnic minorities.”

A quarter also comes from volunteers who live below the poverty line.

And also one in four belongs to people over 65 years of age.

Analysis of this unpublished material has already revealed the existence of 275 million unknown genetic variants.

“Each of them offers possible new clues to understand and cure some of the most critical diseases in the world,” says Bick, of Vanderbilt University, in the city of Nashville.

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The doctor gives an example from his laboratory.

His team has taken advantage of the immense diversity of the project to find a mutation that protects against chronic kidney disease associated with the APOL1 gene, a phenomenon more frequently 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 complicated puzzles, it is very important to have very large data sets, not just diverse ones,” argues Bick.

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 the 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 ones,” explains the American researcher.

His results are published this Monday in the magazine

Nature

, standard of the best world science.

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 8, he emigrated with his family to the United States, after the Cuban Revolution.

The doctor highlights the historical lack of diversity in genomic research and affirms that more than 90% of the studies have been done with populations with European ancestors.

Medications that don't work

Pérez-Stable recalls the case of clopidogrel, an antiplatelet medication that is used to prevent blood clots in patients who have suffered a heart attack or stroke, or have circulation problems in their arms and legs.

“Clopidogrel does not work when a person has a genetic change that affects the processing of the medication.

And it turns out that most people of Hawaiian or Pacific Island origin do not process it, so it does not work in those populations as indicated,” warns the Cuban-American doctor.

Three years ago, a court ordered the pharmaceutical companies Bristol Myers Squibb and Sanofi to pay almost 800 million euros to the state of Hawaii for marketing clopidogrel in the archipelago, “knowing that it was not effective for many patients,” according to a statement from the prosecution.

The director emphasizes that science has made great discoveries thanks to the inclusion of diverse populations in genetic analyses.

Pérez-Stable himself participated in 2014 in a study that identified a specific mutation (6q25) that reduces the risk of breast cancer by 60% and is only found in Latin American women with indigenous ancestors.

The doctor remembers another case.

The latest drugs to lower bad cholesterol—the so-called PCSK9 inhibitors—were discovered thanks to an African-American family with very low levels of this substance in their blood.

A team of researchers, led by American doctor Helen Hobbs, developed the drugs to mimic the effect seen in the family.

If DNA is imagined as a sequence of chemical letters with the instructions for a person's functioning, epigenetic changes would be like accent marks, capable of modifying the message and triggering disorders, such as cancer.

Pérez-Stable highlights that living conditions, such as poverty, can cause epigenetic changes.

“There are few studies that have the potential to capture this phenomenon and this project is one of them,” she celebrates.

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