Endometriosis could be genetic: First Indian genome study sheds light

For years, women with endometriosis have recounted identical tales to doctors: excruciating menstrual cramps, chronic pelvic pain, and infertility, often after years of suffering and sometimes with a mother or sister experiencing similar symptoms. India's inaugural genome-wide investigation into the disease has unveiled evidence suggesting a genetic predisposition in Indian women, alongside pinpointing genetic markers particularly pertinent to the Indian demographic.

Published in Scientific Reports, the study unveiled 21 suggestive genetic regions linked to endometriosis in Indian women, with the strongest signal situated near the LINC00415/SHISA2 region on chromosome 13. Researchers also detected genetic signals in line with previously recognized endometriosis triggers, and discovered that a risk score crafted from European populations held relevance within the Indian cohort.

However, the findings are not yet primed for clinical application or individual risk forecasting. Nonetheless, researchers posit that they serve as a crucial launching pad for more extensive studies, particularly within South Asian populations that have been sorely underrepresented in genetic research concerning endometriosis. Dr Rahul Gajbhiye, Scientist and Head of the Clinical Research Laboratory at ICMR–National Institute for Research on Women's Health (ICMR–NIRWoH) in Mumbai, and the study's principal investigator, recounted how he was captivated by the myriad women enduring severe menstrual pain, chronic pelvic discomfort, or infertility, despite years of suffering and in some instances, a familial history of similar symptoms.

He noted, "When I commenced working on endometriosis research nearly two decades ago, I was struck by the multitude of women who had suffered in silence for extended periods before receiving a diagnosis." To delve deeper into the genetic underpinnings of endometriosis, Gajbhiye intensified his investigations during his INSA postdoctoral fellowship at the University of Queensland, Australia, from 2017 to 2018.

Following his return to India, he secured a DBT Wellcome India Alliance Clinical and Public Health Intermediate Fellowship in 2019, which facilitated the establishment of the Endometriosis Clinical and Genetic Research in India (ECGRI) initiative and the assembly of a clinical and genomic dataset comprising Indian women. The study engaged 18 centers across the country, uniting gynecological laparoscopic surgeons, clinicians, researchers, and laboratory teams.

Women with surgically confirmed endometriosis and control participants were enlisted from diverse geographical regions and ancestry backgrounds. Lead author Dr Sandhya Anand remarked that the 21 suggestive genetic regions offer a wealth of new leads in comprehending endometriosis among Indian women. "Our findings, while not immediately applicable to clinical testing, constitute a vital groundwork for forthcoming South Asian studies on the biology, genetic susceptibility, and early identification of endometriosis," she emphasized.

Endometriosis, affecting approximately 10% of women of reproductive age, often experiences delayed diagnosis due to symptoms like severe menstrual pain, which are frequently dismissed or deemed normal. Researchers underscore the significance of this issue in India, where awareness, early detection, access to specialized care, and population-specific research evidence remain scarce.

A substantial portion of the existing genetic research on endometriosis has been conducted on populations of European descent. The novel Indian dataset thus contributes a crucial South Asian dimension to global research on the disease. Dr Geetanjali Sachdeva, Director of ICMR–NIRWoH and a co-author, highlighted Gajbhiye's creation of one of the largest Indian endometriosis research datasets, integrating detailed clinical data with genomic information and a dedicated biorepository.

"This platform represents one of the pioneering entities in India for endometriosis research, laying a foundation for future studies on disease mechanisms, risk prediction, non-invasive diagnostics, and translational women's health research," she stated. While the genetic findings cannot presently ascertain whether an individual woman will develop endometriosis, they may ultimately aid scientists in deciphering why certain women are more vulnerable, pinpointing biological pathways implicated in the disease, and exploring novel avenues for earlier diagnosis and treatment.

Gajbhiye expressed optimism, stating that the findings "provide a foundation for larger studies exploring earlier recognition and, eventually, more personalized treatments."