Tackling the Lack of Diversity in Human Genome Collection

Although scientists are making progress, the world's collection of human genome data remains heavily skewed toward those of European ancestry. A 2016 analysis showed that 19 percent of participants in genome-wide association studies (GWAS) were of non-European ancestry, up from 4 percent in 2009. That improvement, though, reflected primarily an increase in several Asian countries. “The degree to which people of African and Latin American ancestry, Hispanic people, and indigenous peoples are represented in GWAS has barely shifted,” noted University of Washington researchers Alice Popejoy and Stephanie Fullerton in their analysis published in Nature. GWAS scan thousands of genomes to identify variants associated with specific diseases.

The National Human Genome Research Institute (NHGRI), for years, has tried to rectify the imbalance by requiring grantees to recruit diverse participants and supporting efforts to reach underrepresented groups. But considering the explosive growth in the number of genomes sequenced—now in the tens of millions—the lack of diversity remains vexing. “This is definitely an important problem, and it is one that the NHGRI is working hard to remedy,” says Andrew Clark, a population geneticist at Cornell University.

The reasons for the overrepresentation of European ancestry are many. Researchers may prefer a homogeneous pool to reduce genetic variance in studies. Members of underrepresented groups may lack access to testing or may be reluctant to participate. To overcome the latter, researchers themselves need to be more diverse and to tailor messages that will show underrepresented participants the benefits of genomic studies, noted a March 2018 Nature Reviews article on prioritizing diversity in genomics research.

Researchers have much to gain by expanding the pool of underrepresented groups. “Given that humans have been diversifying for 200,000 years there is a lot of genetic variation out there. By capturing this variation, we can make conclusions about how genes function and get clues about how biology works,” says Lawrence Brody, director of the genomics and society division of NHGRI.

There is therapeutic value as well. People in underrepresented populations may be missing out on precision medicine therapies to treat both rare genetic disorders and common diseases such as type 2 diabetes, heart disease, and asthma that involve genetic and environmental factors.

For example, there are wide disparities among different populations when it comes to asthma, notes Eimear Kenny, founding director of the Center for Genomic Health at Mount Sinai. Mexicans have among the lowest rates (4 percent) of asthma in the world, whereas Puerto Ricans have one of the highest (18 percent). “If you lump Hispanics/Latinos, you’d miss that completely,” she says. Researchers such as Esteban Burchard, at the University of California, San Francisco, are focusing on how genomics may influence how different racial and ethnic groups respond differently to asthma medications.

The National Heart, Lung, and Blood Instititute, under director Gary Gibbons, is successfully recruiting African Americans to participate in a study of the role of race ancestry in cardiovascular disease and the interplay of genomic variations with environmental factors and social determinants. Gibbons is also involved with the H3Africa initiative, aimed at developing genomics technologies in Africa. To date, 54,000 people in 34 African countries are participating.

In her own lab, Kenny's team draws on data from BioMe biobank, made up of 65 percent of participants of African or Latino ancestry. The team found that a rare genetic disorder called Steel syndrome, associated with very short stature and serious joint problems, is far more common in Puerto Ricans (2 percent) than in the general population. Because this was not recognized before, patients were missing out on diagnosis and treatment.

Other researchers have made discoveries that benefit the general population. It was found that a subset of African Americans carries a mutation in the PCSK9 gene, which causes the allele not to function. Researchers were surprised to learn that people with the mutation had very low levels of both LDL cholesterol levels and heart disease. That led to cholesterol-lowering drugs being developed that mimic the genetic variant. “There is a whole new biological pathway that you would have missed if you had not studied a diverse group of people,” says Brody.

Ultimately, he says, “If we have a big database that is reflective of everyone, the disparity in being able to interpret genetic test results goes away. As it is now, if a person of Hmong ancestry comes in for genetic testing, that person is more likely to receive an inconclusive result than if someone has European ancestry.”

Having a more diverse database is only the beginning, adds Kenny. “It's about the questions being asked, the diseases given prominence, the drug therapies being invested in. It's a first step in a big pipeline about how we think of diversity in terms of human health.”