From Science News:
DNA databases need diversity for genetic research to help all people
A lack of diversity in genetic databases is making precision medicine ineffective for many people.
By Tina Hesman Saey
It’s been two decades since the Human Genome Project first unveiled a rough draft of our genetic instruction book. The promise of that medical moon shot was that doctors would soon be able to look at an individual’s DNA and prescribe the right medicines for that person’s illness or even prevent certain diseases.
That promise, known as precision medicine, has yet to be fulfilled in any widespread way. True, researchers are getting clues about some genetic variants linked to certain conditions and some that affect how drugs work in the body. But many of those advances have benefited just one group: people whose ancestral roots stem from Europe. In other words, white people.
Instead of a truly human genome that represents everyone, “what we have is essentially a European genome,” says Constance Hilliard, an evolutionary historian at the University of North Texas in Denton. “That data doesn’t work for anybody apart from people of European ancestry.”
… Often those genetic databases draw on data mainly from white participants. But race isn’t the issue. The problem is that collectively, those data add up to a catalog of genetic variants that don’t represent the full range of human genetic diversity.
When people of African, Asian, Native American or Pacific Island ancestry get a DNA test to determine if they inherited a variant that may cause cancer or if a particular drug will work for them, they’re often left with more questions than answers. The results often reveal “variants of uncertain significance,” leaving doctors with too little useful information. This happens less often for people of European descent. That disparity could change if genetics included a more diverse group of participants, researchers agree.
One solution is to make customized reference genomes for populations whose members die from cancer or heart disease at higher rates than other groups, for example, or who face other worse health outcomes, Hilliard suggests.
And the more specific the better. For instance, African Americans who descended from enslaved people have geographic and ecological origins as well as evolutionary and social histories distinct from those of recent African immigrants to the United States. Those histories have left stamps in the DNA that can make a difference in people’s health today. The same goes for Indigenous people from various parts of the world and Latino people from Mexico versus the Caribbean or Central or South America.
Researchers have made efforts to boost diversity among participants in genetic studies, but there is still a long way to go.
It’s almost as if the more science-oriented and altruistic volunteers are found among whites …
How to involve more people of diverse backgrounds — which goes beyond race and ethnicity to include geographic, social and economic diversity — in genetic research is fraught with thorny ethical questions.
To bring the public into the conversation, Science News posed some core questions to readers who watched a short video of Hilliard explaining her views.
Again and again, respondents to our unscientific survey said that genetic research is important for improving medical care. But our mostly white respondents had mixed feelings about whether the solution is customized projects such as Hilliard proposes or a more generalized effort to add variants to the existing human reference genome. Many people were concerned that pointing out genetic differences may reinforce mistaken concepts of racial inferiority and superiority, and lead to more discrimination.
In other words, the white readers of Science News worry that more genetic studies on more diverse people would prove The Bell Curve right, and that would the worst thing imaginable.
Why is genetics so white?
Some of our readers asked how genetic research got to this state in the first place. Why is genetic research so white and what do we do about it? …
All humans have basically the same DNA. Any two people are 99.9 percent genetically identical.
Is that number that was popular around 2000 still accurate?
… But the 0.1 percent difference between individuals — all the spelling variations, typos, insertions and deletions sprinkled throughout the text of the human instruction book — contributes to differences in health and disease.
…In 2018, people of European ancestry made up more than 78 percent of GWAS participants, researchers reported in Cell in 2019. That’s an improvement from 2009, when 96 percent of participants had European ancestors, researchers reported in Nature.…
Most of the research funded by the major supporter of U.S. biomedical research, the National Institutes of Health, is done by scientists who identify as white, says Sam Oh, an epidemiologist at the University of California, San Francisco. Black and Hispanic researchers collectively receive about 6 percent of research project grants, according to NIH data.
As usual in 2020 articles about race, Asians are ignored, even when quoting an Asian.
“Generally, the participants who are easier to recruit are people who look like the scientists themselves — people who share similar language, similar culture. It’s easier to establish a rapport and you may already have inroads into communities you’re trying to recruit,” Oh says.
When origins matter
Hilliard’s hypothesis is that precision medicine, which tailors treatments based on a person’s genetic data, lifestyle, environment and physiology, is more likely to succeed when researchers consider the histories of groups that have worse health outcomes. For instance, Black Americans descended from enslaved people have higher rates of kidney disease and high blood pressure, and higher death rates from certain cancers than other U.S. racial and ethnic groups.
In her work as an evolutionary historian studying the people and cultures of West Africa, Hilliard may have uncovered one reason that African Americans descended from enslaved people die from certain types of breast and prostate cancers at higher rates than white people, but have lower rates of the brittle-bone disease osteoporosis. African Americans have a variant of a gene called TRPV6 that helps their cells take up calcium. Overactive TRPV6 is also a hallmark of those breast and prostate cancers that disproportionately kill Black people in the United States.
The variant can be traced back to the ancestors of some African Americans: Niger-Congo–speaking West Africans. In that part of West Africa, the tsetse fly kills cattle, making dairy farming unsustainable. Those ancestral people typically consumed a scant 200 to 400 milligrams of calcium per day. The calcium-absorbing version of TRPV6 helped the body meet its calcium needs, Hilliard hypothesizes. Today, descendants of some of those people still carry the more absorbent version of the gene, but consume more than 800 milligrams of calcium each day.
Assuming that African American women have the same dietary need for calcium as women of European descent may lead doctors to recommend higher calcium intake, which may inadvertently encourage growth of breast and prostate cancers, Hilliard reported in the Journal of Cancer Research & Therapy in 2018.
“Nobody is connecting the dots,” Hilliard says, because most research has focused on the European version of TRPV6. …
Recruiting people from all over the world to participate in genetic research might seem like the way to increase diversity, but that’s a fallacy, Hilliard says. If you really want genetic diversity, look to Africa, she says.
Humans originated in Africa, and the continent is home to the most genetically diverse people in the world. Ancestors of Europeans, Asians, Native Americans and Pacific Islanders carry only part of that diversity, so sequencing genomes from geographically dispersed people won’t capture the full range of variants.
But a lot of the genetic diversity in sub-Saharan Africans doesn’t do much. That’s why they kind of look alike.
… Some countries have begun building specialized reference genomes. China compiled a reference of the world’s largest ethnic group, Han Chinese. A recent analysis indicates that Han Chinese people can be divided into six subgroups hailing from different parts of the country. China’s genome project is also compiling data on nine ethnic minorities within its borders. Denmark, Japan and South Korea also are creating country-specific reference genomes and cataloging genetic variants that might contribute to health problems that their populations face. Whether this approach will improve medical care remains to be seen. …
One big drawback to Hilliard’s proposal may be social rather than scientific, according to some Science News readers.
Many respondents to our survey expressed concern that even well-intentioned scientists might do research that ultimately increases bias and discrimination toward certain groups. As one reader put it, “The idea of diversity is being stretched into an arena where racial differences will be emphasized and commonalities minimized. This is truly the entry to a racist philosophy.”
If humanity is not allowed to collect massive amounts of genetic data on non-whites, then The Bell Curve can’t be proven true. And that must be the human race’s highest priority, preserving the tiny bit of self-esteem that blacks have at present.
Another reader commented, “The fear is that any differences that are found would be exploited by those who want to denigrate others.” Another added, “The idea that there are large genetic differences between populations is a can of worms, isn’t it?” …
And issues of privacy become a big deal for small groups, such as the 574 recognized Native American tribal nations in the United States, or isolated religious or cultural groups such as the Amish or Hutterites. If one member of such a group decides to give DNA to a genetic project, that submission may paint a genetic portrait of every member of the group. Such decisions shouldn’t be left in individual hands, Tsosie says; it should be a community decision.
My impression is that the Amish enthusiastically participate in genetic research. From Wikipedia:
Amish represent a collection of different demes or genetically closed communities. Since almost all Amish descend from about 500 18th-century founders, genetic disorders that come out due to inbreeding exist in more isolated districts (an example of the founder effect). These disorders include dwarfism (Ellis–van Creveld syndrome), Angelman syndrome, and various metabolic disorders, as well as an unusual distribution of blood types. Some of these disorders are quite rare, or unique, and are serious enough to increase the mortality rate among Amish children. The majority of Amish accept these as “Gottes Wille” (God’s will); they reject use of preventive genetic tests prior to marriage and genetic testing of unborn children to discover genetic disorders. However, Amish are willing to participate in studies of genetic diseases. Their extensive family histories are useful to researchers investigating diseases such as Alzheimer’s, Parkinson’s, and macular degeneration.
Back to Science News:
Hilliard says minorities’ resistance to participating in genetic research is about more than a fear of being singled out; it’s the result of being experimented on but seeing medical breakthroughs benefit only white people.
The use of DNA from relatives to find murderers and rapists in recent years probably discourages blacks. To whites, the idea of my DNA being used to arrest some 4th cousin for some ghastly crime seems like justice. To blacks, it seem like a way to put a first cousin who is turning his life around in the pen.