Endometriosis is a gynaecological condition in which tissue like endometrium grows outside the uterus, affecting 247 million women globally, including 42 million in India. Endometriosis impacts overall well-being by affecting mental and physical health with chronic pelvic pain, menstrual disturbances and fertility issues. With 50% risk attributed to genetic factors, GWAS have identified 42 risk loci; however, populations represented are mainly European, with limited studies on Asian populations. Overall, Indian ancestry remains significantly underrepresented in genetic studies, limiting the global understanding of genetic diversity.
Under the Endometriosis Clinical and Genetic Research in India (ECGRI) study, we conducted the first GWAS of endometriosis in an Indian population, addressing a critical gap in global endometriosis research. A total of 2,523 participants representing diverse geographic regions and ethnic backgrounds across India were genotyped using the Illumina GSA platform, processed under stringent quality control protocols and imputed with the SEAD reference panel.
Association testing was performed in PLINK using an additive model adjusted for age, batch effects, heterozygosity, and population structure. Analysis identified 88 suggestive SNPs (p<1×10⁻⁵) across 21 genomic loci. A novel locus on Chromosome 13 showed the strongest association (p<1×10⁻⁶). Functional annotation highlighted regulatory roles for key variants, including SNPs in enhancers upstream of SHISA2, implicating pathways involved in Wnt signalling. Six SNPs from the European meta-analysis replicated with consistent direction of effect and nominal significance (p<0.05). Asian ancestry meta-analysis combining our dataset with the Japanese GWAS identified 31 genome-wide significant SNPs (p<1×10⁻⁸) across Chr1 and Chr9, replicating known associations near WNT4 and CDKN2B-AS1, providing evidence that risk loci are shared across ancestries.
The study identifies novel and shared loci of endometriosis and highlights potential target genes for functional and translational research, advancing global understanding of genetic risk and laying the groundwork for larger-scale studies in Indian and South Asian populations.