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Independent Replication and Meta-Analysis for Endometriosis Risk Loci

  • Yadav Sapkota (a1), Amelie Fassbender (a2) (a3), Lisa Bowdler (a1), Jenny N. Fung (a1), Daniëlle Peterse (a2) (a3), Dorien O (a2) (a3), Grant W. Montgomery (a1), Dale R. Nyholt (a1) (a4) and Thomas M. D'Hooghe (a2) (a3) (a5)...


Endometriosis is a complex disease that affects 6–10% of women in their reproductive years and 20–50% of women with infertility. Genome-wide and candidate-gene association studies for endometriosis have identified 10 independent risk loci, and of these, nine (rs7521902, rs13394619, rs4141819, rs6542095, rs1519761, rs7739264, rs12700667, rs1537377, and rs10859871) are polymorphic in European populations. Here we investigate the replication of nine SNP loci in 998 laparoscopically and histologically confirmed endometriosis cases and 783 disease-free controls from Belgium. SNPs rs7521902, rs13394619, and rs6542095 show nominally significant (p < .05) associations with endometriosis, while the directions of effect for seven SNPs are consistent with the original reports. Association of rs6542095 at the IL1A locus with ‘All’ (p = .066) and ‘Grade_B’ (p = .01) endometriosis is noteworthy because this is the first successful replication in an independent population. Meta-analysis with the published results yields genome-wide significant evidence for rs7521902, rs13394619, rs6542095, rs12700667, rs7739264, and rs1537377. Notably, three coding variants in GREB1 (near rs13394619) and CDKN2B-AS1 (near rs1537377) also showed nominally significant associations with endometriosis. Overall, this study provides important replication in a uniquely characterized independent population, and indicates that the majority of the original genome-wide association findings are not due to chance alone.


Corresponding author

address for correspondence: Yadav Sapkota, Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston 4006 Queensland, Australia. E-mail:


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Twin Research and Human Genetics
  • ISSN: 1832-4274
  • EISSN: 1839-2628
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