Lack Of Diversity In Genetic Databases Hampers Research

Aug 22, 2019
Originally published on August 30, 2019 12:30 pm

When Lalita Manrai went to see her doctor for treatment of kidney disease, she noticed that some of the blood test results had different "normal" ranges for African Americans compared with everybody else.

When she asked her doctor which range applied to her — a woman born in India — he said the "everybody else" category was actually based on a study of Europeans, so neither category was right.

Instead, he said, he calculated "normal" for her by averaging the two values.

"It's ridiculous," says Arjun Manrai, a medical researcher at Harvard Medical School, who recounted this story of his mother, who died in 2018. But there simply isn't good information about a lot of medical issues that may vary based on a person's ancestry. "In this vacuum of information, this was what [the doctor] was doing as his approach to staging her kidney disease," Manrai says.

It's important to get those laboratory results right, because they influence a patient's treatment, Manrai says.

The same problem comes up in other common situations, such as the A1C test that is used to diagnose and manage diabetes, and in genetic variants that can identify people at risk of sudden death from heart disease.

These factual gaps exist because much of the research used to understand these genetic tests and lab values comes from predominantly European populations. Manrai is part of a growing effort to correct the skewed picture that results.

One of the most widely used resources for studying the genetics of disease is the U.K. Biobank, which contains samples from half a million middle-aged British people, 95% of whom are of European ancestry.

"At the time they were recruited and the age group that were recruited, that largely reflected the average across the U.K.," says Dr. Cathie Sudlow, the biobank's chief scientist. "So because the study was in the U.K., that's what we got."

The biobank has been a boon to scientists who want to identify the genes that are involved in disease. Genes are universal. But the ethnically skewed resource doesn't work as well to identify the genetic variants that differ based on ancestry.

"There is no one cohort anywhere in the world that can answer all questions for all people," Sudlow says. So the biobank is working to help develop much more diverse resources.

The U.K. Biobank has helped establish large repositories in Mexico and China. In the United States, Sudlow and her colleagues have been offering advice to the National Institutes of Health, which is gradually putting together a biobank that aims to have a diverse population of a million volunteers.

There are dozens and dozens of collections like this scattered around the world, some in private hands and others accessible to scientists. Nobody knows exactly how many of these collections exist, but "broadly we're talking about at least millions of people," says Ewan Birney, co-director of the European Bioinformatics Institute.

He is part of an effort to find ways to link some of these resources together so scientists can quickly see how a discovery in one group applies to people with different ancestries. Birney says even though most of the initial work has been in European populations, a lot of it is relevant to everybody.

"How genetics works in different countries — sort of a surprise — is that very often the genetics is pretty much the same as you move between different countries," Birney says.

Where biobank study conclusions can be misleading is in the details. The same genes and proteins are involved in diseases such as diabetes, but the variants that can affect a person's risk of disease differ based on a person's genetic heritage.

Birney expects that the new and linked databases not only will help identify issues of concern to a particular ethnic group but will identify genes that are important for everybody's health. He's particularly eager to learn what comes out of a biobank project taking shape in sub-Saharan Africa.

"Because Africa is the birthplace of humans, there's the highest amount of genetic diversity inside of sub-Saharan Africa," he says. "And it's really clear if you are a geneticist, we should be spending an awful lot more time studying humans there."

Birney is mindful of simply allowing scientists from rich companies to swoop in on this resource, so right now the African scientists developing biobanks will have an opportunity to study the data first. Birney says it's "really important that we do that in a way that is empowering and enabling for the scientists who come from these different countries."

Manrai at Harvard is tapping into data that's already available, including medical databases curated by the National Institutes of Health and the Centers for Disease Control and Prevention.

"I think understanding ancestry, race, ethnicity is an area that we're going to see a tremendous amount of work in over the next 10 years," he says.

You can contact NPR Science Correspondent Richard Harris at rharris@npr.org.

Copyright 2019 NPR. To see more, visit https://www.npr.org.

AILSA CHANG, HOST:

Millions of people around the world have donated DNA samples and medical records to researchers. They form the foundation of the science of so-called precision medicine. To date, most of the results have been based on samples from people of European ancestry. Scientists are now working to correct the skewed picture that results in. NPR's science correspondent Richard Harris explains.

RICHARD HARRIS, BYLINE: When you get lab results from your doctor, you may have noticed that some of them specify different normal ranges depending on your race. Arjun Manrai says for people with kidney disease, those details can really matter.

ARJUN MANRAI: You can change the stage of kidney disease that you have and when we start initiating things like dialysis.

HARRIS: Manrai studies health genetics at Harvard Medical School, but he also has a personal story about his mother, who was born in India, immigrated to the United States and, later in life, developed kidney disease. Her lab results showed normal ranges for blacks and everybody else. But her doctor explained that the everybody-else category was really based on results from Europeans.

MANRAI: So my mom responded to her nephrologist like, hey. Well, you know, you have this African American range. You have this white range. I'm an Indian American woman. Which of these ranges actually should I be using? He responded that, you know, you're not either of these two, so I averaged the two numbers for you. And it just...

HARRIS: That's ridiculous, isn't it?

MANRAI: It's ridiculous. But in the absence, I'd say in this kind of vacuum of information, this was what he was doing as his approach to staging her kidney disease.

HARRIS: Doctors don't have good information about people of different ancestries because so much of the basic science has been done on samples drawn from European populations. One of the most widely used repositories is called the U.K. Biobank, which contains samples from half a million middle-aged Brits. Chief scientist Cathie Sudlow says 95% came from white Europeans.

CATHIE SUDLOW: At the time that they were recruited and the age group that were recruited, that largely reflected the average across the UK. So because the study was in the U.K., that's what we got.

HARRIS: The Biobank has been a boon to scientists who want to identify the genes that are involved in disease. Genes are universal, but it doesn't work to identify all the genetic variants that differ based on ancestry.

SUDLOW: There is no one cohort anywhere in the world that can answer all questions for all people. And one of the really important things about some of the - what the U.K. Biobank's now engaged in with others in the U.S. and, indeed, throughout the world is to look at ways in which data from different ethnic groups can learn from each other.

HARRIS: The U.K. Biobank has helped establish large repositories in Mexico and in China. In the U.S., the National Institutes of Health is gradually putting together a biobank that aims to have a diverse population of a million volunteers. There are dozens and dozens of collections like this scattered around the world; some in private hands, others accessible to scientists.

EWAN BIRNEY: Broadly, we're talking about at least millions of people.

HARRIS: Ewan Birney, co-director of the European Bioinformatics Institute, is part of an effort to find ways to link some of these together so scientists can quickly see how a discovery in one group applies to people with different ancestries. Birney says even though most of the initial work has been in European populations, a lot of it is relevant to everyone.

BIRNEY: How genetics works in different countries - sort of a surprise is that very often, the genetics is pretty much the same as you move between different countries.

HARRIS: Where it breaks down is in the details. The same genes and proteins are involved in, say, diabetes, but the variants differ based on a person's genetic heritage. Birney expects that the new databases will not only help identify issues of concern to a particular ethnic group but can identify genes that are important for everybody's health. He's particularly eager to learn what comes out of a biobank project taking shape in sub-Saharan Africa.

BIRNEY: Because Africa is the birthplace of humans, there's just the highest amount of genetic diversity inside of sub-Saharan Africa. And it's really clear, if you're a geneticist, we should be spending an awful lot more time studying humans there. But then that also is really important that we do that in a way which is empowering and enabling of the scientists who come from these different countries.

HARRIS: The African scientists will get a chance to do their own research before opening this resource up to the rest of the world, Birney says. Arjun Manrai at Harvard is tapping into data that's already available, as he works to make sure that genetic tests and lab results aren't skewed by a person's ancestry.

MANRAI: I think understanding ancestry, race, ethnicity is an area that we're going to see a tremendous, tremendous amount of work in over the next 10 years.

HARRIS: And he says these new resources will help a lot.

Richard Harris, NPR News. Transcript provided by NPR, Copyright NPR.