Journal article
A multi-level investigation of the genetic relationship between endometriosis and ovarian cancer histotypes
S Mortlock, RI Corona, PF Kho, P Pharoah, JH Seo, ML Freedman, SA Gayther, MT Siedhoff, PAW Rogers, R Leuchter, CS Walsh, I Cass, BY Karlan, BJ Rimel, GW Montgomery, K Lawrenson, SP Kar
Cell Reports Medicine | CELL PRESS | Published : 2022
Abstract
Endometriosis is associated with increased risk of epithelial ovarian cancers (EOCs). Using data from large endometriosis and EOC genome-wide association meta-analyses, we estimate the genetic correlation and evaluate the causal relationship between genetic liability to endometriosis and EOC histotypes, and identify shared susceptibility loci. We estimate a significant genetic correlation (rg) between endometriosis and clear cell (rg = 0.71), endometrioid (rg = 0.48), and high-grade serous (rg = 0.19) ovarian cancer, associations supported by Mendelian randomization analyses. Bivariate meta-analysis identified 28 loci associated with both endometriosis and EOC, including 19 with evidence for..
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Awarded by Ovarian Cancer Research Alliance
Funding Acknowledgements
We would like to thank the research participants and employees of 23andMe for making this work possible. We would like to acknowledge the International Endometriosis Genetics Consortium and Ovarian Cancer Association Consortium for their contributions generating the GWASdatasets and data access. We are grateful to the thousands of patients who donated the specimens that enable this research to happen. For specific acknowledgments for the endometriosis meta-analysis, please see Sapkota et al.<SUP>17</SUP> For specific acknowledgments for the ovarian cancer meta-analysis, please see Phelan et al.<SUP>18</SUP> The GTEx Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. The data used for the analyses described in this manuscript were obtained from the GTEx Portal on 06/26/20. This work was supported by the National Health and Medical Research Council of Australia (GNT1026033, GNT1105321, GNT1147846, Investigator Grant 1177194 to G.W.M. and Medical Research Future Fund Research grant MRF1199785 to S.M.) and National Institutes of Health (R01CA193910, R01CA204954, R01CA211707, R01CA251555). S.P.K. is supported by a United Kingdom Research and Innovation Future Leaders Fellowship (MR/T043202/1). K.L. is supported by a Liz Tilberis Early Career Award (599175) and a Program Project Development (373356) from the Ovarian Cancer Research Alliance, plus a Research Scholar's Grant from the American Cancer Society (134005). For funding details of the endometriosis meta-analysis, please see Sapkota et al.<SUP>17</SUP> For funding details of the ovarian cancer metaanalysis, please see Phelan et al.<SUP>18</SUP>