NEW YORK – Researchers from the GenomeAsia 100K Project have begun to develop a reference dataset of genomes from individuals living in Asia, with the goal of boosting the representation of Asians in genomic research.
Currently, about 6 percent of the sequenced human genomes are from Asian individuals, even though about half the world's population is Asian. The GenomeAsia 100K Project — which was established in 2016 and consists of Singapore's Nanyang Technological University and its industry partners Genentech, Macrogen, and Medgenome — aims to eventually sequence the genomes of 100,000 individuals living in Asia to close that gap.
The consortium has so far sequenced 1,739 individuals from more than 200 populations and 64 countries in Asia. In its pilot study, published today in Nature, the consortium reported on how the addition of genomic data from Asian populations has given it insights into previously unappreciated population structure as well as clarified the implications of certain genetic variations.
"We are deciphering the genetic fabric of Asians," co-author Jeong-Sun Seo, the chairman of Macrogen, said in a statement.
The researchers sequenced the genomes of 1,739 individuals to an average 36x coverage. These samples came from individuals living throughout Asia, including not only China and India, but also Malaysia, South Korea, and the Philippines, among dozens of other countries. The researchers focused on gathering samples from individuals from remote and isolated communities, as well as from various caste and language groups.
Using a combination of principal component, admixture, and other analyses, the researchers found that their samples largely reflected previous Asian population structure studies. For instance, they reported that India, Indonesia, and Malaysia encompass multiple ancestral populations and multiple admixture groups.
But they also found that certain populations in India, Indonesia, and Malaysia that have been grouped together anthropologically are more closely related genetically to their geographic neighbors than to other populations in that anthropological group, suggesting that the darker skin color common among members of those groups is likely due to environmental adaptation, rather than shared ancestry.
The researchers also uncovered varying levels of ancestry derived from the ancient Denisovans in Asian populations, and estimated that Melanisians and the Aeta have the highest portion of Denisovan ancestry.
Meanwhile, the researchers reported that these additional Asian genome sequences can aid medical genetic studies. Nearly a quarter of protein-altering variants within their dataset were not present in public databases like the Exome Aggregation Consortium (ExAC), gnomAD, the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project (ESP), and dbSNP.
These databases, the researchers noted, are often used to filter out common alleles in studies of rare genetic disease that are likely not disease causing. When they added their dataset to gnomAD to filter a set of exomes from the Indian Maturity Onset Diabetes in the Young (MODY) project, the researchers could reduce the number of candidate variants to pursue by twofold. In particular, they uncovered a common polymorphism in NEUROD1 that was previously reported to be medically relevant but is likely benign, based on the addition of their dataset.
Additionally, they noted that variants affecting sensitivity to the blood thinner warfarin appear to be more common among individuals from South Korea, China, Japan, and Mongolia.
The consortium plans to continue to collect and analyze additional samples. Stephan Schuster, a professor at NTU, noted that knowing people's genetic background is an important part of being able to practice personalized medicine. "For precision medicine to be precise, you need to know precisely who you are," he said in a statement.
Macrogen has further announced that it plans to develop a direct-to-consumer genetic testing service based on this data and a "Global Clinical Genome Supermarket" service for medical professionals.