Genetic research now seeks diversity
The evening began with samosas and tea and a recitation of a verse from the Koran, first in Arabic, then in the English translation.
Then, inside the banquet hall at Santa Clara’s Muslim Community Association, UCSF oncologist Pamela Munster asked the crowd of more than 100 Bay Area residents:
“Who here is worried about having cancer? Who’s had anyone in the family who had cancer? Did you ever wonder why?”
As a smattering of hands went up, Munster continued, “We’re hoping to provide some answers.”
Some genetic mutations, such as BRCA1 and BRCA2, can be a risk factor for developing hereditary cancers, Munster explained using slides on a projector.
The Friday night event, held at one of the largest Muslim community centers in California, was organized by UCSF and Color Genomics, a Burlingame company that sells DNA tests that analyze 30 genes linked to common hereditary cancers including breast, ovarian and pancreatic cancer. Genetic counselors from UCSF and Color were on hand to demonstrate how to use the
saliva kits so participants could take the test themselves.
While learning about about their own genetic risks, they could also contribute to a scientific goal.
For months, Color and UCSF have been hosting similar events across the Bay Area — at a synagogue, an African American church and a Latino community center — to recruit members of those historically underrepresented communities to submit saliva samples. The goal is to collect 500 samples, split evenly among people of African, Asian, European and Hispanic descent. The campaign strives to solve a diversity problem: 80 percent of people whose DNA has been analyzed in scientific research on genetic variants linked to disease are of European descent. Similarly, most published studies on human genomics have analyzed the genetics of people of European ancestry.
“There’s a gap in the knowledge for other, non-European groups,” said Alicia Zhou, head of research at Color Genomics.
Many diseases are known to be more prevalent in some ethnic groups than others, such as some cancers in Asian and African American populations. And some ethnic groups are more prone to genetic variants that can render medications less effective or lead to a higher likelihood of developing certain diseases. Having a more diverse database of genomic information could lead to a better understanding and ability to treat diseases across ethnic groups.
Color’s event at the Muslim Community Association prompted 60 people to participate in the study, including Habiba Nasseri. The 43-yearold Santa Clara resident said she does not have a family history of cancer — except for one cousin with breast cancer — but she sees value in improving scientific knowledge about genetic similarities and differences among populations.
“The world is so large, we’re all genetically connected somehow,” Nasseri said. “If it doesn’t help me out, it’ll help my kids or grandkids. It’ll help benefit research for future generations — everyone’s kids and everyone’s grandkids.”
Once all 500 samples are collected, Color’s lab will analyze the anonymous aggregate data with the intention of publishing the information at a conference. The company provides the tests, which normally sell for $249, to participants for free.
One commonly cited analysis in Nature, from 2009, found that 96 percent of participants in genome variant studies were of European descent. Since then, the proportion has improved slightly to about 80 percent, according to an updated analysis published in 2016. But progress is not advancing quickly enough, some experts said.
The Exome Aggregation Consortium, a publicly available research database out of MIT and Harvard with sequencing data of 60,000 people, has just 5,000 samples from people of African descent and 4,000 from people of East Asian descent.
“This is a tremendous problem the field of genomics faces,” said Adam Auton, senior statistical geneticist at Mountain View’s 23andMe, which sells kits that test for genetic variants linked to celiac disease, Parkinson’s, lateonset Alzheimer’s and other diseases.
Prior to joining 23andMe, Auton studied genetic variations in human populations as an assistant professor at Albert Einstein College of Medicine. He said the disparity is structural: When proposing a new study, it’s often easier to get funding to study populations that have already been studied.
“From an ethical standpoint it’s indefensible,” Auton said. “From a scientific standpoint it’s also indefensible. The genetic diversity in European populations only represents a small subset of global genetic diversity. By not studying the complete spectrum of human diversity, there’s a huge risk we’ll be missing many of the discoveries that could be beneficial for all humans across the globe.”
23andMe recently completed enrollment for a project, backed by a $1.7 million grant from the National Institutes of Health, to recruit 2,000 African Americans to create a dataset that will help researchers better understand patterns of genetic variation, company officials said. The information will be included in the NIH’s data depository, where it will be available for researchers.
Gaining data from 2,000 people may not seem like a huge number, Auton said, but it’s four times larger than the largest publicly available database of human genetic variation, the 1000 Genomes Project, which contains 500 genomes of people of African descent. The project is a global academic initiative created in 2008 to sequence the genomes of 1,000 people from around the world, and the information is made available to scientists to use in their own genetic research.
The human genome is more than 99 percent identical in all people regardless of their ancestry. Genetic variants are not uncommon and do not necessarily indicate medical problems. But some variants are mutations that heighten the risk for developing some cancers, or render some drug less effective.
In 2014, the attorney general of Hawaii sued drugmakers Bristol-Myers Squibb and Sanofi over the labeling of the blood-thinning drug Plavix. The drug was problematic for many people of East Asian and Pacific Islander descent — a large portion of the state’s population — because they carry a variant of a liver enzyme that makes it harder to properly metabolize the drug. Marketing the drug in Hawaii put the population at risk for gastrointestinal bleeding and other health complications, according to the suit, which is ongoing. A Sanofi spokeswoman said the Plavix label includes information about the metabolism of the drug in patients of different ethnic groups. A spokeswoman for Bristol-Myers Squibb declined to comment.
“That’s an example where lack of diversity with respect to genetic and biomedical research can lead to tragic outcomes,” said Dr. Esteban Burchard of UCSF, who studies genetic risk factors for disease in ethnically diverse populations.