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. 

Phelan CM, Kuchenbaecker KB, Tyrer JP, Kar SP, Lawrenson K, Winham SJ, Dennis J, Pirie A, Riggan MJ, Chornokur G, Earp MA, Lyra PC, Lee JM, Coetzee S, Beesley J, McGuffog L, Soucy P, Dicks E, Lee A, Barrowdale D, Lecarpentier J, Leslie G, Aalfs CM, Aben KKH, Adams M, Adlard J, Andrulis IL, Anton-Culver H, Antonenkova N, , Aravantinos G, Arnold N, Arun BK, Arver B, Azzollini J, Balmaña J, Banerjee SN, Barjhoux L, Barkardottir RB, Bean Y, Beckmann MW, Beeghly-Fadiel A, Benitez J, Bermisheva M, Bernardini MQ, Birrer MJ, Bjorge L, Black A, Blankstein K, Blok MJ, Bodelon C, Bogdanova N, Bojesen A, Bonanni B, Borg Å, Bradbury AR, Brenton JD, Brewer C, Brinton L, Broberg P, Brooks-Wilson A, Bruinsma F, Brunet J, Buecher B, Butzow R, Buys SS, Caldes T, Caligo MA, Campbell I, Cannioto R, Carney ME, Cescon T, Chan SB, Chang-Claude J, Chanock S, Chen XQ, Chiew YE, Chiquette J, Chung WK, Claes KBM, Conner T, Cook LS, Cook J, Cramer DW, Cunningham JM, D'Aloisio AA, Daly MB, Damiola F, Damirovna SD, Dansonka-Mieszkowska A, Dao F, Davidson R, DeFazio A, Delnatte C, Doheny KF, Diez O, Ding YC, Doherty JA, Domchek SM, Dorfling CM, Dörk T, Dossus L, Duran M, Dürst M, Dworniczak B, Eccles D, Edwards T, Eeles R, Eilber U, Ejlertsen B, Ekici AB, Ellis S, Elvira M, , Eng KH, Engel C, Evans DG, Fasching PA, Ferguson S, Ferrer SF, Flanagan JM, Fogarty ZC, Fortner RT, Fostira F, Foulkes WD, Fountzilas G, Fridley BL, Friebel TM, Friedman E, Frost D, Ganz PA, Garber J, García MJ, Garcia-Barberan V, Gehrig A, , Gentry-Maharaj A, Gerdes AM, Giles GG, Glasspool R, Glendon G, Godwin AK, Goldgar DE, Goranova T, Gore M, Greene MH, Gronwald J, Gruber S, Hahnen E, Haiman CA, Håkansson N, Hamann U, Hansen TVO, Harrington PA, Harris HR, Hauke J, , Hein A, Henderson A, Hildebrandt MAT, Hillemanns P, Hodgson S, Høgdall CK, Høgdall E, Hogervorst FBL, Holland H, Hooning MJ, Hosking K, Huang RY, Hulick PJ, Hung J, Hunter DJ, Huntsman DG, Huzarski T, Imyanitov EN, Isaacs C, Iversen ES, Izatt L, Izquierdo A, Jakubowska A, James P, Janavicius R, Jernetz M, Jensen A, Jensen UB, John EM, Johnatty S, Jones ME, Kannisto P, Karlan BY, Karnezis A, Kast K, , Kennedy CJ, Khusnutdinova E, Kiemeney LA, Kiiski JI, Kim SW, Kjaer SK, Köbel M, Kopperud RK, Kruse TA, Kupryjanczyk J, Kwong A, Laitman Y, Lambrechts D, Larrañaga N, Larson MC, Lazaro C, Le ND, Le Marchand L, Lee JW, Lele SB, Leminen A, Leroux D, Lester J, Lesueur F, Levine DA, Liang D, Liebrich C, Lilyquist J, Lipworth L, Lissowska J, Lu KH, Lubinnski J, Luccarini C, Lundvall L, Mai PL, Mendoza-Fandiño G, Manoukian S, Massuger LFAG, May T, Mazoyer S, McAlpine JN, McGuire V, McLaughlin JR, McNeish I, Meijers-Heijboer H, Meindl A, Menon U, Mensenkamp AR, Merritt MA, Milne RL, Mitchell G, Modugno F, Moes-Sosnowska J, Moffitt M, Montagna M, Moysich KB, Mulligan AM, Musinsky J, Nathanson KL, Nedergaard L, Ness RB, Neuhausen SL, Nevanlinna H, Niederacher D, Nussbaum RL, Odunsi K, Olah E, Olopade OI, Olsson H, Olswold C, O'Malley DM, Ong KR, Onland-Moret NC, , Orr N, Orsulic S, Osorio A, Palli D, Papi L, Park-Simon TW, Paul J, Pearce CL, Pedersen IS, Peeters PHM, Peissel B, Peixoto A, Pejovic T, Pelttari LM, Permuth JB, Peterlongo P, Pezzani L, Pfeiler G, Phillips KA, Piedmonte M, Pike MC, Piskorz AM, Poblete SR, Pocza T, Poole EM, Poppe B, Porteous ME, Prieur F, Prokofyeva D, Pugh E, Pujana MA, Pujol P, Radice P, Rantala J, Rappaport-Fuerhauser C, Rennert G, Rhiem K, Rice P, Richardson A, Robson M, Rodriguez GC, Rodríguez-Antona C, Romm J, Rookus MA, Rossing MA, Rothstein JH, Rudolph A, Runnebaum IB, Salvesen HB, Sandler DP, Schoemaker MJ, Senter L, Setiawan VW, Severi G, Sharma P, Shelford T, Siddiqui N, Side LE, Sieh W, Singer CF, Sobol H, Song H, Southey MC, Spurdle AB, Stadler Z, Steinemann D, Stoppa-Lyonnet D, Sucheston-Campbell LE, Sukiennicki G, Sutphen R, Sutter C, Swerdlow AJ, Szabo CI, Szafron L, Tan YY, Taylor JA, Tea MK, Teixeira MR, Teo SH, Terry KL, Thompson PJ, Thomsen LCV, Thull DL, Tihomirova L, Tinker AV, Tischkowitz M, Tognazzo S, Toland AE, Tone A, Trabert B, Travis RC, Trichopoulou A, Tung N, Tworoger SS, van Altena AM, Van Den Berg D, van der Hout AH, van der Luijt RB, Van Heetvelde M, Van Nieuwenhuysen E, van Rensburg EJ, Vanderstichele A, Varon-Mateeva R, Vega A, Edwards DV, Vergote I, Vierkant RA, Vijai J, Vratimos A, Walker L, Walsh C, Wand D, Wang-Gohrke S, Wappenschmidt B, Webb PM, Weinberg CR, Weitzel JN, Wentzensen N, Whittemore AS, Wijnen JT, Wilkens LR, Wolk A, Woo M, Wu X, Wu AH, Yang H, Yannoukakos D, Ziogas A, Zorn KK, Narod SA, Easton DF, Amos CI, Schildkraut JM, Ramus SJ, Ottini L, Goodman MT, Park SK, Kelemen LE, Risch HA, Thomassen M, Offit K, Simard J, Schmutzler RK, Hazelett D, Monteiro AN, Couch FJ, Berchuck A, Chenevix-Trench G, Goode EL, Sellers TA, Gayther SA, Antoniou AC, Pharoah PDP. 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. 

Kar SP, Beesley J, Amin Al Olama A, Michailidou K, Tyrer J, Kote-Jarai Z, Lawrenson K, Lindstrom S, Ramus SJ, Thompson DJ, , Kibel AS, Dansonka-Mieszkowska A, Michael A, Dieffenbach AK, Gentry-Maharaj A, Whittemore AS, Wolk A, Monteiro A, Peixoto A, Kierzek A, Cox A, Rudolph A, Gonzalez-Neira A, Wu AH, Lindblom A, Swerdlow A, , , Ziogas A, Ekici AB, Burwinkel B, Karlan BY, Nordestgaard BG, Blomqvist C, Phelan C, McLean C, Pearce CL, Vachon C, Cybulski C, Slavov C, Stegmaier C, Maier C, Ambrosone CB, Høgdall CK, Teerlink CC, Kang D, Tessier DC, Schaid DJ, Stram DO, Cramer DW, Neal DE, Eccles D, Flesch-Janys D, Edwards DR, Wokozorczyk D, Levine DA, Yannoukakos D, Sawyer EJ, Bandera EV, Poole EM, Goode EL, Khusnutdinova E, Høgdall E, Song F, Bruinsma F, Heitz F, Modugno F, Hamdy FC, Wiklund F, Giles GG, Olsson H, Wildiers H, Ulmer HU, Pandha H, Risch HA, Darabi H, Salvesen HB, Nevanlinna H, Gronberg H, Brenner H, Brauch H, Anton-Culver H, Song H, Lim HY, McNeish I, Campbell I, Vergote I, Gronwald J, Lubinski J, Stanford JL, Benítez J, Doherty JA, Permuth JB, Chang-Claude J, Donovan JL, Dennis J, Schildkraut JM, Schleutker J, Hopper JL, Kupryjanczyk J, Park JY, Figueroa J, Clements JA, Knight JA, Peto J, Cunningham JM, Pow-Sang J, Batra J, Czene K, Lu KH, Herkommer K, Khaw KT, , Matsuo K, Muir K, Offitt K, Chen K, Moysich KB, Aittomäki K, Odunsi K, Kiemeney LA, Massuger LF, Fitzgerald LM, Cook LS, Cannon-Albright L, Hooning MJ, Pike MC, Bolla MK, Luedeke M, Teixeira MR, Goodman MT, Schmidt MK, Riggan M, Aly M, Rossing MA, Beckmann MW, Moisse M, Sanderson M, Southey MC, Jones M, Lush M, Hildebrandt MA, Hou MF, Schoemaker MJ, Garcia-Closas M, Bogdanova N, Rahman N, , Le ND, Orr N, Wentzensen N, Pashayan N, Peterlongo P, Guénel P, Brennan P, Paulo P, Webb PM, Broberg P, Fasching PA, Devilee P, Wang Q, Cai Q, Li Q, Kaneva R, Butzow R, Kopperud RK, Schmutzler RK, Stephenson RA, MacInnis RJ, Hoover RN, Winqvist R, Ness R, Milne RL, Travis RC, Benlloch S, Olson SH, McDonnell SK, Tworoger SS, Maia S, Berndt S, Lee SC, Teo SH, Thibodeau SN, Bojesen SE, Gapstur SM, Kjær SK, Pejovic T, Tammela TL, , , Dörk T, Brüning T, Wahlfors T, Key TJ, Edwards TL, Menon U, Hamann U, Mitev V, Kosma VM, Setiawan VW, Kristensen V, Arndt V, Vogel W, Zheng W, Sieh W, Blot WJ, Kluzniak W, Shu XO, Gao YT, Schumacher F, Freedman ML, Berchuck A, Dunning AM, Simard J, Haiman CA, Spurdle A, Sellers TA, Hunter DJ, Henderson BE, Kraft P, Chanock SJ, Couch FJ, Hall P, Gayther SA, Easton DF, Chenevix-Trench G, Eeles R, Pharoah PD, Lambrechts D. Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types. Cancer Discov [print-electronic]. 2016 Sep; 6(9): 1052-67. PMID: 27432226, PMCID: PMC5010513, PII: 2159-8290.CD-15-1227, DOI: 10.1158/2159-8290.CD-15-1227, ISSN: 2159-8290.