Published Sep 15, 2026 | 4:15 PM ⚊ Updated Sep 15, 2026 | 4:15 PM
Endometriosis is a disease in which tissue similar to the endometrium—the lining of the uterus—grows elsewhere in the body.
Synopsis: Researchers studying endometriosis in Indian women have identified 21 genetic regions that may be linked to the disease. The strongest signal points towards a possible connection involving the thyroid-related gene SHISA2, offering new clues to the disease’s biology. However, the findings need further research and independent confirmation.
Researchers have mapped 21 genetic regions that may raise the risk of endometriosis in Indian women, marking the first genome-wide study of the disease in this population.
The study, published in Scientific Reports, draws on the Endometriosis Clinical and Genetic Research in India (ECGRI) consortium. Researchers recruited women from 18 sites across the country, covering public and private tertiary-care centres.
“Through the ECGRI initiative, this nationwide study generated the first genome-wide evidence on genetic susceptibility to endometriosis in Indian women,” ICMR’s National Institute for Research on Women’s Health said in a statement.
Endometriosis occurs when tissue similar to the lining of the uterus grows outside it, often causing pelvic pain, disrupting periods and contributing to infertility.
The condition affects about one in 10 women of reproductive age worldwide. India accounts for an estimated 50 million cases, nearly 18% of the global burden.
Despite that burden, Indian women have been largely missing from genetic studies of endometriosis. Most previous research has drawn on women of European and East Asian ancestry, leaving a gap in what scientists know about the genetic factors at play in South Asian women.
Researchers recruited 1,383 women with surgically confirmed endometriosis and 1,388 women without the condition. After checking the quality of the genetic data, they retained 2,523 participants for the main analysis: 1,288 cases and 1,235 controls.
Participants came from five regions, representing Indo-European, Dravidian, and Tibeto-Burmese ancestry groups. Most women with endometriosis in the study had advanced disease, with 85.5% of the cases classified as stage III or IV.
Researchers then scanned genetic material to find differences that showed up more often in women with endometriosis.
“We conducted a GWAS in 2523 participants from a nationwide, multicentre endometriosis case–control study in India,” the authors wrote. A GWAS, or genome-wide association study, looks across a person’s genetic material to find variations that occur more often among people with a particular condition. “Genetic susceptibility in Indian women showed both shared features with other populations and evidence of potential population-specific signals.”
Also Read: Male infertility treatment costs rival endometriosis in India
The analysis identified 88 genetic variants across regions that showed a possible link with endometriosis.
Researchers stopped short of calling these 21 regions confirmed risk factors. The signals crossed a preliminary statistical threshold that flags a finding worth investigating, but none met the stricter standard scientists use to confirm a genetic association.
“Twenty-one loci demonstrated suggestive associations,” the authors noted in their summary. “No variant reached genome-wide significance in the discovery cohort alone.”
Researchers said the modest size of the Indian study, compared with much larger international genetic studies, may have limited their ability to detect stronger signals.
Also Read: Patients are bringing AI diagnoses to fertility clinics
The standout signal emerged from chromosome 13, where the variant rs35236165 turned up within a long non-coding RNA called LINC00415. The region also sits close to regulatory elements linked to a gene called SHISA2.
“The strongest signal mapped to chromosome 13 within a long non-coding RNA and in regulatory elements upstream of SHISA2,” the authors wrote in the abstract. “Colocalization analysis showed shared genetic effects with SHISA2 expression in thyroid tissue and methylation sites in the endometrium.”
In simpler terms, the genetic signal linked with endometriosis also appeared connected with how SHISA2 behaves in thyroid tissue. Researchers also found a link with chemical changes that can influence gene activity in the lining of the uterus.
SHISA2 plays a role in biological pathways that help regulate cell behaviour, including WNT signalling and fibroblast growth factor pathways. Earlier research also reported higher SHISA2 activity during one phase of the menstrual cycle in women with endometriosis.
Previous clinical studies have reported an association between thyroid dysfunction and endometriosis. This study does not show that thyroid disease causes endometriosis, or that endometriosis causes thyroid disease. It offers a genetic clue that may help explain the association between the two.
“Our study provides the first genetic evidence that may implicate thyroid-mediated regulatory mechanisms in endometriosis susceptibility,” the authors wrote in their discussion.
Also Read: Working night shifts regularly? It may be harming your fertility
Researchers then checked whether genetic variants already linked to endometriosis in other populations also showed up in Indian women.
Of 46 risk variants identified in a European GWAS, 38 turned up in the Indian dataset or matched closely related variants. Seven showed the same direction of effect in the Indian cohort, involving regions near WNT4, DNM3, KDR, 7p15.2, CDKN2B-AS1, RNLS and VEZT.
Several of these variants proved far more, or far less, common in Indian women than in European populations. Such differences help explain why a genetic signal found in one population may not appear in another.
The finding also underlined why researchers keep pushing for genetic studies that include more diverse populations rather than leaning on European datasets alone.
Also Read: Can you get pregnant with PCOS?
The team next tested a polygenic risk score, which combines the effects of many genetic variants to estimate a person’s inherited risk of a disease.
The score, originally built from European data, also tracked with endometriosis in the Indian cohort. Women in the highest tenth of genetic risk carried almost four times the risk seen among women in the lowest tenth.
“A polygenic risk score derived from European populations demonstrated comparable predictive performance in the Indian cohort,” the authors wrote.
The score also moved with disease severity. Women with stage III or IV endometriosis had higher average scores than those with stage I or II disease.
To strengthen the analysis, researchers combined their Indian data with results from a Japanese GWAS. The combined dataset covered 3,074 women with endometriosis and 82,210 controls.
This analysis identified 31 variants that reached genome-wide significance, clustered in two regions: one near WNT4 on chromosome 1 and the other near CDKN2B-AS1 on chromosome 9. Earlier studies had already linked both regions to endometriosis.
“Meta-analysis with a Japanese GWAS replicated two known genome-wide significant associations near WNT4 and CDKN2B-AS1, supporting shared genetic susceptibility across populations,” the authors wrote.
Different variants emerged as the strongest signals in the Indian and Japanese datasets, yet both linked closely to signals already reported in European studies. Researchers read this as evidence that some of the biology behind endometriosis holds across populations.
The team stopped short of calling the 21 newly identified regions confirmed risk factors.
The findings remain hypothesis-generating: they point to possible biological links that still need testing. The study lacked a large, independent South Asian group that could confirm the signals.
“The 21 suggestive associations identified in the Indian discovery GWAS should be considered hypothesis-generating and require independent replication before being regarded as confirmed endometriosis susceptibility loci,” the authors wrote.
The chromosome 13 region near SHISA2 remains the strongest candidate for further research, backed by several lines of evidence linking it to gene regulation and changes in the endometrium.
India carries a heavy caseload of endometriosis, yet Indian women have had limited representation in studies probing the genetic roots of the disease.
“Genetic studies indicate substantial heritability, yet genome-wide association studies (GWAS) have predominantly focused on European populations, with limited evidence from South Asian groups,” the authors wrote.
The ECGRI study set out to begin closing that gap, examining genetic risk among women from different parts of India and across different ancestry groups.
“This work strengthens India’s contribution to global women’s health and public-health research, and builds an evidence base for early recognition, risk prediction and personalised care,” ICMR-NIRWoH said in its statement.
Researchers said larger studies involving South Asian women, stronger population-specific genetic databases and further laboratory research will be needed to confirm the findings.
For now, the 21 regions stand as clues rather than clinical markers. But the chromosome 13 finding raises a fresh question: whether genetic changes involving SHISA2 and thyroid-related pathways could help explain part of the biology behind endometriosis.
