An international effort to sequence the genomes of Asian populations in order to generate a comprehensive map of genetic diversity in the region is likely to graduate to microarray-powered genome-wide association studies in the future.
The Human Genome Organization's Pan-Asian Population Genomics Initiative, or PAPGI, is currently gathering whole-genome sequence data submitted by members from 16 countries, and aims to begin analyzing that data by this fall with plans to publish the findings sometime next year, according to steering committee member Jong Bhak.
Bhak, who is director of the Korean Genome Research Foundation in Seoul, told BioArray News this week that PAPGI researchers intend to use the data in GWAS to identify variants linked to traits found in their particular population of interest.
"Once we have whole-genome sequences, we will select variants that are candidates for certain phenotypes," said Bhak. He said that the first, sequencing-based phase of the project will allow PAPGI members to identify common, benign variants found in Asian populations, as well as to identify potentially pathogenic variants.
"We will try to produce detailed chip-based data and analyses after collecting many common and rare variants from the genome data," said Bhak. In Korea, Bhak said that he and fellow researchers are particularly interested in variants associated with olfactory receptors and diet.
Fahd Al-Mulla, head of molecular pathology at Kuwait University, said that he would like to use the new whole-genome population data in a similar manner, but will focus on health issues specific to the Middle East.
According to Al-Mulla, up to 30 percent of the population in the Gulf states have type 2 diabetes. "If we compare the genomes of Arabs to other eastern Asian populations where diabetes is not so prevalent, then a better understanding of the genetic variations may lead to better and stronger genotype-phenotype associations," he said.
Al-Mulla and colleagues will also look to use the new data for cancer-related studies. Occurrences of cancer in general are low in the Gulf states, according to Al-Mulla. He said that the rate of colorectal cancer in Kuwait is 19 cases per 100,000 individuals annually, where as the rate in the West is up to three times that.
Al-Mulla and other researchers in the Middle East have joined together to form Genome Arabia, which is generating whole-genome sequencing data on local populations to carry out these studies (BAN 4/30/2013).
"Looking for population-specific variation is vital to understand the influence of mutations in a specific population," Al-Mulla said. "One should not depend on data from other populations to argue that the genetic change found in a certain disease is causative," he said. "Generally, this is the reason why GWAS data failed to detect genetic associations with diseases in some countries."
Toward its goals, Al-Mulla said that his lab has already genotyped 80 Arabs from Kuwait using the Affymetrix SNP 6.0 and is "aiming to have more done in the near future." On its website, PAPGI suggests using the SNP 6.0 or Illumina's Omni2.5 BeadChip as part of these initial genotyping studies, but Bhak said that even higher-resolution arrays could be used. "The idea is to use the latest and largest possible, even exome chips," he said.
One consistent critique of catalog whole-genome arrays, such as the SNP 6.0 or the Omni2.5, is that they were optimized for use with European populations. Bhak noted that the assembled database of the different PAPGI populations could be used to design chips for future association studies.
Whole-genome sequencing and high-density genotyping arrays are a step up in terms of complexity from the 50,000-marker SNP array that PAPGI's predecessor effort, the Pan-Asia SNP Initiative, used to produce information supporting the major southern migration theory of Asian ethnic groups, results that were published in Science in December 2009.
According to a statement provided to BioArray News by PAPGI's steering commitee, PAPGI "expands on the strengths" of PASNPi and aims at "unraveling the patterns of genomic diversity that modulate phenotypic traits," contributing "much-needed genetic clues to influence healthcare interventions and shed new lights on human evolution and migration in this geographic area."
Stressing its transparency, PAPGI said in the statement that all generated data and resources will be "made available to the worldwide scientific community on completion of the project, marked by the consortium’s first publication." More than 100 whole genomes and exomes from various populations have already been collected, PAPGI said, and it expects to release the first data from the initiative by the end of this year.
Bhak portrayed PAPGI as having numerous goals. While PAPGI aims to produce as much genome data as possible to map target populations, he said that the initiative is also helping to develop Asian scientific infrastructure.
"The future of genomics will probably [be] led by Asian scientists in the next several decades," he said. "I think this work will be one of the early demonstrations [of] Asian collaboation."
Al-Mulla voiced similar hopes for the effort.
"Examining national and local genomes is a good thing for genomic medicine and individualized therapies," he said. PAPGI "will give us more information on human migration, ancestries, and tracking human genomic variations and genotype-phenotype relationships," he said. "It will be of great benefit because we will have a wider view of the human genome variations from an Asian perspective."