Endogamy, the age-old practice of marrying within small communities, can lead to population-specific genetic diseases in India, a research study conducted by Hyderabad-based Centre for Cellular and Molecular Biology (CCMB) has revealed.
Researchers have found a significant number of disease-causing genetic variants, many of which are unique to specific populations. The study analysed genes of South Indian populations suggests a high inbreeding rate of nearly 60 per cent.
Led by CSIR fellow Bhatnagar and senior scientist Dr K Thangaraj, the research team analysed 281 high-coverage whole exome sequences from four anthropologically distinct populations, revealing the profound genetic consequences of endogamy.
One of the key findings of this study was identifying that the widespread prevalence of ‘ankylosing spondylitis’, a type of arthritis that causes inflammation in the joints and ligaments of the spine, is linked to the ‘HLA-B27:04 risk allele’, a genetic variant that increases the likelihood of developing a disease.
“We found a high incidence of ankylosing spondylitis disease in the Reddy community, who dwell in a specific geographical region of Andhra Pradesh,” said rheumatologist Sarath Chandra Mouli Veeravalli from Krishna Institute of Medical Sciences (KIMS), Hyderabad, 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 said.
“We examined several key factors, such as the extent of inbreeding and novel genetic variants in populations. We also looked at pharmacogenomic markers that influence drug metabolism to understand why different drugs seem to work differently in different populations,” lead author Pratheusa Machha said.
The research, published in the Journal of Genetics and Genomics, 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.
The study targeted communities where medical understanding is limited or where there’s a lack of records for early childhood deaths.
The 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 drugs 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.
Also read: The environment friendly Karens of the Andamans
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.
Follow us
