The diversity of Asian genomes

In a pilot study, researchers looked at more than 1’200 whole-genome sequences from individuals representing hundreds of population groups across Asia, and compared them with existing sequence data from almost 600 African, European and American individuals, according to a new report in Nature Online.

Individuals of Asian descent, who make up about half the global population, have been severely underrepresented in human genetic studies. As a side note, the same applies to individuals of African descent as well. This limits the applicability of existing results for a large part of the world.

The GenomeAsia 100K project seeks to address this disparity. A non-profit international consortium established in 2016, its members include Singapore’s Nanyang Technological University and industry partners such as South Korean biotech firm Macrogen and California-based MedGenome Inc. The consortium’s initial goal is to sequence the genomes of 100’000 Asians and make the data available through a public database for use by researchers and pharmaceutical companies.

At the beginning of the this project the assumption was that Asian genetic variation would be more or less a subset of what’s already been deciphered in the European population. That turned out to be not true.

For the pilot study, the consortium team examined genome sequences representing people living in dozens of countries including China, India, Indonesia, Japan, the Philippines, Malaysia, Mongolia, Pakistan, Papua New Guinea and Russia, as well as samples representing minorities living in remote and isolated communities or belonging to various caste and language groups. The team found that nearly a quarter of the protein-altering gene variants in their Asian dataset were not present in currently available public databases such as the 1000 Genomes Project and the Exome Aggregation Consortium. Most of the new variants were rare, yet more than 140’000 variants occurred in more than 1% of people in specific populations.

In rare disease genetics,  common variants are usually eliminated as suspects in searches for genes potentially involved in a disease, so these new examples can aid in such studies among Asian populations. Awareness of genetic variants that affect an individual’s response to certain drugs is also important in tailoring treatment and conducting clinical trials, the researchers note. For example, they found that carbamezepine, clopidigrel, peginterferon and warfarin showed the largest variation between populations in predicted adverse drug responses with groups ranging from 0 and 100 predicted adverse drug responses. Thus, the HLA-B*15:02 variant, associated with risk for development of Steven Johnson Syndrome in patients treated with carbamazepine was found to occur at an increased frequency in Austronesian language-speaking populations from southeast Asia (for example, 63% in the Mentawai of West Sumatra; 46.6% in the Nias of North Sumatra) compared with other groups. There are roughly 400 million individuals who belong to Austronesian groups that are at increased risk for carbamazepine sensitivity, including the vast majority of the people from Indonesia, Malaysia and the Philippines.

Asians have been cut off from advances in genetics and genomics that have taken place especially over the last 10 years. The study, published in Nature Online in December 2019, is a first step to provide the tools so that Asians also have access to genetic information about disease and disease risk that is available now in Caucasian populations.