We have developed several phenotyping approaches within electronic health record (EHR) populations to identify pregnancy outcomes and gynecologic complications in efforts to collaborate with several large-scale consortiums, as well as to build resources for future genetic studies. These studies have included work in pelvic organ prolapse, endometriosis, and ovarian cancer. We are actively looking for further opportunities to build resources for additional studies in reproductive genetics using EHR populations and data we have developed are available for collaboration.
Pelvic Organ Prolapse:
We have developed a phenotyping approach to identify pelvic organ prolapse cases (POP) to conduct genetic studies of POP using EHR data in collaboration with investigators at UNC and VUMC. These studies have included epidemiologic, gene environment, and GWAS analyses using BioVU and the Women’s Health Initiative data. We are currently developing a manuscript describing our phenotyping with POP and a study evaluating BMI x genotype interactions on POP outcomes.
Relevant Publications:
Giri A, Hartmann KE, Hellwege JN, Velez Edwards DR, Edwards TL. Obesity and pelvic organ prolapse: a systematic review and meta-analysis of observational studies. Am. J. Obstet. Gynecol [print-electronic]. 2017 Jul; 217(1): 11-26.e3. PMID: 28188775, PII: S0002-9378(17)30174-6, DOI: 10.1016/j.ajog.2017.01.039, ISSN: 1097-6868.
Giri A, Wu JM, Ward RM, Hartmann KE, Park AJ, North KE, Graff M, Wallace RB, Bareh G, Qi L, O'Sullivan MJ, Reiner AP, Edwards TL, Velez Edwards DR. Genetic Determinants of Pelvic Organ Prolapse among African American and Hispanic Women in the Women's Health Initiative. PLoS ONE. 2015; 10(11): e0141647. PMID: 26545240, PMCID: PMC4636147, PII: PONE-D-15-26602, DOI: 10.1371/journal.pone.0141647, ISSN: 1932-6203.
Wu JM, Ward RM, Allen-Brady KL, Edwards TL, Norton PA, Hartmann KE, Hauser ER, Velez Edwards DR. Phenotyping clinical disorders: lessons learned from pelvic organ prolapse. Am. J. Obstet. Gynecol [print-electronic]. 2013 May; 208(5): 360-5. PMID: 23200709, PMCID: PMC3597745, PII: S0002-9378(12)02085-6, DOI: 10.1016/j.ajog.2012.11.030, ISSN: 1097-6868.
Giri A, Hartmann KE, Aldrich MC, Ward RM, Wu JM, Park AJ, Graff M, Qi L, Nassir R, Wallace RB, O'Sullivan MJ, North KE, Velez Edwards DR, Edwards TL. Admixture mapping of pelvic organ prolapse in African Americans from the Women's Health Initiative Hormone Therapy trial. PLoS ONE. 2017; 12(6): e0178839. PMID: 28582460, PMCID: PMC5459562, PII: PONE-D-16-33760, DOI: 10.1371/journal.pone.0178839, ISSN: 1932-6203.
Ward RM, Velez Edwards DR, Edwards T, Giri A, Jerome RN, Wu JM. Genetic epidemiology of pelvic organ prolapse: a systematic review. American journal of obstetrics and gynecology. 2014; 211(4):326-35. NIHMSID: NIHMS597466, PMID 24721264, PMCID:PMC4213176
Endometriosis:
We have ongoing collaborative work with an endometriosis consortium to conduct both GWAS and exome chip analysis of endometriosis risk. We have identified and contributed endometriosis samples from BioVU to these efforts.
Relevant Publications:
Sapkota Y, Vivo I, Steinthorsdottir V, Fassbender A, Bowdler L, Buring JE, Edwards TL, Jones S, O D, Peterse D, Rexrode KM, Ridker PM, Schork AJ, Thorleifsson G, Wallace LM, , Kraft P, Morris AP, Nyholt DR, Edwards DRV, Nyegaard M, D'Hooghe T, Chasman DI, Stefansson K, Missmer SA, Montgomery GW. Analysis of potential protein-modifying variants in 9000 endometriosis patients and 150000 controls of European ancestry. Sci Rep. 2017 Sep 9/12/2017; 7(1): 11380. PMID: 28900119, PMCID: PMC5595920, PII: 10.1038/s41598-017-10440-9, DOI: 10.1038/s41598-017-10440-9, ISSN: 2045-2322.
Sapkota Y, Steinthorsdottir V, Morris AP, Fassbender A, Rahmioglu N, De Vivo I, Buring JE, Zhang F, Edwards TL, Jones S, O D, Peterse D, Rexrode KM, Ridker PM, Schork AJ, MacGregor S, Martin NG, Becker CM, Adachi S, Yoshihara K, Enomoto T, Takahashi A, Kamatani Y, Matsuda K, Kubo M, Thorleifsson G, Geirsson RT, Thorsteinsdottir U, Wallace LM, , Yang J, Velez Edwards DR, Nyegaard M, Low SK, Zondervan KT, Missmer SA, D'Hooghe T, Montgomery GW, Chasman DI, Stefansson K, Tung JY, Nyholt DR. Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism. Nat Commun. 2017 May 5/24/2017; 8: 15539. PMID: 28537267, PMCID: PMC5458088, PII: ncomms15539, DOI: 10.1038/ncomms15539, ISSN: 2041-1723.
Ovarian Cancer:
We are currently contributing genotype data from the BioVU DNA Resource at Vanderbilt University Medical Center to the Ovarian Cancer Consortium (OCAC). Dr. Velez Edwards is the site PI for the BVU data being contributed to OCAC. We contributed 449 ovarian cancer cases and 545 controls, which are now redeposited in BioVU and available for future studies in BioVU. We are also collaborating with Dr. Alicia Beeghly-Fadiel on studies looking at ovarian cancer survival. We welcome any collaborations to expand analyses of these data for genetic studies in BioVU. Ongoing collaboration with OCAC consortium and studies evaluating differential genetically predicted gene expression within our local BioVU ovarian cancer data.
Relevant Publications:
Glubb DM, Johnatty SE, Quinn MCJ, O'Mara TA, Tyrer JP, Gao B, Fasching PA, Beckmann MW, Lambrechts D, Vergote I, Velez Edwards DR, Beeghly-Fadiel A, Benitez J, Garcia MJ, Goodman MT, Thompson PJ, Dörk T, Dürst M, Modungo F, Moysich K, Heitz F, du Bois A, Pfisterer J, Hillemanns P, , Karlan BY, Lester J, Goode EL, Cunningham JM, Winham SJ, Larson MC, McCauley BM, Kjær SK, Jensen A, Schildkraut JM, Berchuck A, Cramer DW, Terry KL, Salvesen HB, Bjorge L, Webb PM, Grant P, Pejovic T, Moffitt M, Hogdall CK, Hogdall E, Paul J, Glasspool R, Bernardini M, Tone A, Huntsman D, Woo M, Group A, deFazio A, Kennedy CJ, Pharoah PDP, MacGregor S, Chenevix-Trench G. Analyses of germline variants associated with ovarian cancer survival identify functional candidates at the 1q22 and 19p12 outcome loci. Oncotarget. 2017 Sep 9/12/2017; 8(39): 64670-84. PMID: 29029385, PMCID: PMC5630285, PII: 18501, DOI: 10.18632/oncotarget.18501, ISSN: 1949-2553.
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Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer. Nat. Genet [print-electronic]. 2017 May; 49(5): 680-91. PMID: 28346442, PII: ng.3826, DOI: 10.1038/ng.3826, ISSN: 1546-1718.
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