A scientific endeavour to improve representation of whole genome sequences from Asia in global population studies has thrown up many surprises, including discovery of many new gene variants that predispose Asians to diseases such as cancer and diabetes. More importantly, it also showed that a commonly-used anti-convulsant drug can have adverse effects if used on a section of Asian people, whose numbers are around 400 million.

There has been a far cry for increasing the representation of genomic data from Asia, which accounts for 60 per cent of the world’s population. Much of DNA chips used for detecting a person's vulnerability to certain diseases will not work well for Asians as these chips are designed using genomic data derived from non-Asian individuals.

Rich source of information

To correct this, a consortium of scientists, including those from India, other Asian countries and the US, embarked on an ambitious programme to map the genes of as many as 10,0000 Asians. The first set of data they published, as they completed the sequencing of nearly one-fifth of their target, is a rich source of genetic information on Asians, the scientists said, in a paper published in the journal Nature on Wednesday.

In the study, the largest number of individuals whose genomes were sequenced are from India — 598. Most of the DNA samples were collected over the last 30 years by Partha Majumder, renowned population geneticist with the National Institute of Biomedical Genomics in Kalyani in West Bengal, who is a senior author of the Nature study. In addition, the scientists mapped an additional 1,267 DNA samples collected from other major Asian countries. According to the scientists, the samples represented as many as 219 different populations, including 55 ethnic groups in India. Majumder is hopeful that the consortium would be able to reach their target of 10,000 Asian genomes in the next two years.

Identifying variants

The scientists, for instance, have been able to identify variants that predispose individuals to higher risk of cancer, and once this part of the work is expanded, the data from the study can be used to screen individuals to understand the disease risk and provide appropriate monitoring and proactive treatment.

“Similarly, we found variants linked to increase the adverse effect in individuals of certain drugs. Understanding this will allow doctors to provide alternative safer drugs to such patients,” said Somasekar Seshagiri, a scientist with the Chennai-based SciGenom Research Foundation, another senior author of the study.

One such drug was carbamezepine, which is used for treating convulsion and certain other mental disorders. The team found that the drug can have adverse effects on 400 million people belonging to Austronesian language groups. The Austronesian languages are widely spoken throughout Maritime South-East Asia, Madagascar and the islands of the Pacific Ocean.

The study is clinically relevant because 63 million DNA variations discovered by them are an important resource for identifying disease-relevant variants in Indians. “We are now applying the variation data produced in this study to analyse over 1500 familial inherited disorder cases from India,” said Seshagiri.

Recently, V Mohan, a co-author of this study, and his colleagues, at the Madras Diabetes Research Foundation, Chennai, used the variation database from this study in their analysis and identified genetic alterations that contribute to maturity onset diabetes of the young (MODY) in South India.