Endogamy, the practice of marrying within small communities, can lead to population-specific genetic diseases in India, according to a study led by K. Thangaraj, a senior scientist with the CSIR-Centre for Cellular and Molecular Biology (CCMB).
The study analysed 281 high-coverage whole exome sequences from four anthropologically distinct populations, revealing the extent of inbreeding and novel genetic variants.
The research, published in the Journal of Genetics and Genomics, also examined pharmacogenomic markers to understand variations in drug metabolism across different populations. (Pharmacogenomic markers are genetic variations that influence how a person’s body processes and responds to medications. These markers can help assess whether a drug will be effective, how high the risk of side effects might be, and what the optimal dosage could be for an individual.)
“We also looked at pharmacogenomic markers that influence drug metabolism to understand why different drugs seem to work differently in different populations,” Pratheusa Machha, a lead author of the study, said.
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The study targeted communities where medical understanding is limited or where there’s a lack of records for early childhood deaths. It identified a high incidence of ‘ankylosing spondylitis’ in the Reddy community of Andhra Pradesh, according to Sarath Chandra Mouli Veeravalli, Rheumatologist from the Hyderabad-based Krishna Institute of Medical Sciences, and one of the authors of this study.
“This study serves as a ‘proof of concept’ for further investigation, with ongoing research aimed at understanding the genetic basis of the country’s unique genetic structure and developing effective diagnostic and therapeutic approaches,” Thangaraj told businessline.
How a drug works in different people
This study also uncovered novel genetic variants associated with drug metabolism, with implications for personalised medicine, especially in response to some of the common drugs, such as tacrolimus (an immunosuppressive drug) and warfarin (an anticoagulant drug).
“We observed genetic variations in the genes that alter the drug response, which differ across populations, and hence provide opportunity for developing targeted drug and improving health outcomes”, Divya Tej Sowpati, co-author of the study, said.
“Our study forecasts the impact of endogamy in causing population-specific genetic diseases and drug responses. This calls for appropriate genetic screening, counselling, and clinical care for communities vulnerable to various health conditions,” Thangaraj pointed out.
Vinay K. Nandicoori, Director of CCMB, said that the study was a major step towards the understanding of the genetic underpinnings for India’s unique genetic architecture.
“This is important for the development of more effective diagnostic and therapeutic strategies,” he said.