Genome-wide association analysis of endometriosis in Indian women supports shared genetic susceptibility and suggestive population specific signals

Endometriosis is an estrogen-dependent, chronic gynaecological disorder affecting approximately 10% of women of reproductive age and is associated with pelvic pain, infertility, and reduced quality of life. Genetic studies indicate substantial heritability, yet genome-wide association studies (GWAS) have predominantly focused on European populations, with limited evidence from South Asian groups. We conducted a GWAS in 2523 participants from a nationwide, multicentre endometriosis case–control study in India. Genetic susceptibility in Indian women showed both shared features with other populations and evidence of potential population-specific signals. Twenty-one loci demonstrated suggestive associations ( p < 1 × 10⁻ 5 ). The strongest signal mapped to chromosome 13 within a long non-coding RNA and in regulatory elements upstream of SHISA2 . Colocalization analysis showed shared genetic effects with SHISA2 expression in thyroid tissue and methylation sites in the endometrium. A polygenic risk score derived from European populations demonstrated comparable predictive performance in the Indian cohort. Meta-analysis with a Japanese GWAS replicated two known genome-wide significant associations near WNT4 and CDKN2B-AS1 , supporting shared genetic susceptibility across populations. No variant reached genome-wide significance in the discovery cohort alone. This study highlights the importance of expanding genetic studies to diverse populations to improve generalisable genetic risk estimates, biological understanding and equitable precision medicine in women’s health.

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Journal
Scientific Reports
Published
2026-09-05
DOI
https://doi.org/10.1038/s41598-026-69642-9
Primary Topic
Endometriosis Research and Treatment
Type
article
Field-Weighted Citation Impact
0.00

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article

Genome-wide association analysis of endometriosis in Indian women supports shared genetic susceptibility and suggestive population specific signals

Kedar Padte, Bimal John, Reji Mohan, Rahul Gajbhiye et al.
Scientific Reports
Endometriosis Research and Treatment
article

Genome-wide association analysis of endometriosis in Indian women supports shared genetic susceptibility and suggestive population specific signals

Kedar Padte, Bimal John, Reji Mohan, Rahul Gajbhiye, Pramathes DasMahapatra, Sandhya Anand, Grant W. Montgomery, Milind Shah, Smita D. Mahale, Pushplata Sankhwar, Geetanjali Sachdeva, S. K. Mahobia, Sally Mortlock, Hrishikesh Munshi, MR Pai, Nagendra Sardeshpande, Atul Ganatra, Nayna Barada, Chaitanya Shembekar, Gita D. Mishra, Pranay Phukan, Nilajkumar Bagde, Anil Humane, Niraj Mahajan, Sonal Kumta, Shashank Shekhar, Shagufta Khan, Tabassum Khan, Sakshi Gangurde, Ketki Kulkarni, Deepali Kale
article en

Abstract

Endometriosis is an estrogen-dependent, chronic gynaecological disorder affecting approximately 10% of women of reproductive age and is associated with pelvic pain, infertility, and reduced quality of life. Genetic studies indicate substantial heritability, yet genome-wide association studies (GWAS) have predominantly focused on European populations, with limited evidence from South Asian groups. We conducted a GWAS in 2523 participants from a nationwide, multicentre endometriosis case–control study in India. Genetic susceptibility in Indian women showed both shared features with other populations and evidence of potential population-specific signals. Twenty-one loci demonstrated suggestive associations ( p < 1 × 10⁻ 5 ). The strongest signal mapped to chromosome 13 within a long non-coding RNA and in regulatory elements upstream of SHISA2 . Colocalization analysis showed shared genetic effects with SHISA2 expression in thyroid tissue and methylation sites in the endometrium. A polygenic risk score derived from European populations demonstrated comparable predictive performance in the Indian cohort. Meta-analysis with a Japanese GWAS replicated two known genome-wide significant associations near WNT4 and CDKN2B-AS1 , supporting shared genetic susceptibility across populations. No variant reached genome-wide significance in the discovery cohort alone. This study highlights the importance of expanding genetic studies to diverse populations to improve generalisable genetic risk estimates, biological understanding and equitable precision medicine in women’s health.

Scientific Reports
All India Institute of Medical Sciences Raipur (IN), National Institute for Research in Reproductive Health (IN), The University of Queensland (AU), Government Medical College (IN), Shreemati Nathibai Damodar Thackersey Women's University (IN), All India Institute of Medical Sciences Jodhpur (IN), Indian Navy (IN), Almas Hospital (IN), Aditya Jyot Eye Hospital (IN), King George's Medical University (IN), Topiwala National Medical College & BYL Nair Charitable Hospital (IN), Indian Council of Medical Research (IN), Government Medical College and Hospital (IN), Spectrum Clinical Research (India) (IN), Sickle Cell Institute Chhattisgarh, Raipur (IN), Fortis Hospital (IN), Omega Consult (Slovenia) (SI), Hospital Materno-Infantil (ES), Australian e-Health Research Centre (AU), Foundation for Medical Research (IN), Sikkim Manipal University (IN), Assam Medical College (IN), Aalborg University (DK)
Department of Biotechnology, Ministry of Science and Technology, India, Indian Council of Medical Research, University of New South Wales, Novo Nordisk, The Wellcome Trust DBT India Alliance, Novo Nordisk Fonden, Medical Research Council, National Health and Medical Research Council
Gender equality
Openalex Percentile: Top 9%
Endometriosis Research and Treatment
DOIOpen Access PDFOpenAlex
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