Disease causing variants in India differ from Western population: study

Of the 200 participants, 26 per cent found to be carriers of one or more rare genetic disorders, 6 per cent identified as carriers for congenital deafness and 4.5 per cent carriers for cystic fibrosis

A pilot study to determine carrier frequency for common genetic disorders has showed a higher than expected carrier frequency for certain disorders, contrary to the generally held view about their low prevalence in Asian Indians.

Another interesting finding was that disease causing variants observed for certain disorders were different from those seen in Western populations.

The pilot study was conducted by MedGenome Labs, in partnership with Sir Ganga Ram Hospital, New Delhi, over a period of 22 months with a sample size of 200 unrelated individuals, in the North Indian population. After pre-test genetic counselling, the 200 individuals were screened for pathogenic variants in shortlisted 88 genes using Next Generation Sequencing (NGS) technology.

These variants were classified as per the guidelines of American College of Medical Genetics. The study was facilitated by MedGenome Laboratories Bangalore, who carried out the molecular analysis, using NGS and the data was re-analysed at Sir Ganga Ram Hospital, New Delhi.

As per the release, out of the 200 participants, 52 (26 per cent) were found to be carriers of one or more rare genetic disorders, 12 individuals (6 per cent) were identified to be carriers for congenital deafness and the 9 individuals (4.5 per cent)  were observed to be carriers for cystic fibrosis. Three individuals were detected to be carriers for Pompe disease. This study showed a higher carrier frequency for these disorders which was contrary to the generally held view about their low prevalence in Asian Indians.

Another interesting finding was that the disease causing variants observed for disorders such as deafness, cystic fibrosis, Pompe disease, Canavan disease, primary hyperoxaluria, junctional epidermolysis bullosa, galactosemia, medium chain acyl CoA deficiency etc. were different from what is seen in the Western population. Thus, this pilot study highlights the importance of having a Genetic Variant Database for the Indian population.

Dr Sunita Bijarnia-Mahay, author and Senior Consultant, Institute of Medical Genetics & Genomics, Sir Ganga Ram Hospital, New Delhi said, “This study brought surprises by detecting those genetic disorders like cystic fibrosis which were not thought to be common! In future, such NGS based screening tests will bring benefit to not only the young couples who would be planning a baby, but also the healthcare officials in charting out the prevention strategies for our Indian population.”

While carrier screening is being implemented globally to decrease the burden of genetic disease, there is currently no such programme in India, except for limited screening for Thalassemia and Down syndrome. 

According to Dr Sheetal Sharda, Senior Consultant in Clinical Genetics, MedGenome Labs, Bangalore, “Couples may not even be aware that they could be carrying a genetic variant, which could lead to their unborn child developing a genetic disorder. In most cases, carriers of a genetic disorder are asymptomatic and may have no family history and unfortunately their carrier status is often confirmed only after an affected baby is born.”

The release points out that techniques such as NGS could help reduce the burden of genetic disorders in India, more so since over the past few years, the cost of NGS also has come down significantly and continues to fall. More doctors are now aware of NGS and its benefits and relying on them for genetic diagnosis.

According to Prof. IC Verma, Senior Consultant & Advisor, Institute of Medical Genetics & Genomics, Sir Ganga Ram Hospital, New Delhi “In countries such as India with high rates of consanguinity and endogamy, there is inadequate data present on mutations in the community. NGS which sequences the whole genome is better than targeted panels which would miss out on many mutations.  All high risk couples such as in IVF pregnancies, consanguineous couples and those with previous history of abnormal babies must get carrier testing done before their next pregnancy to prevent the birth of babies with genetic disorders and reduce the associated socioeconomic burden.”