Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.
Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mut...
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Public Library of Science (PLoS)
2016-01-01
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| author | Elena Vigorito Karoline B Kuchenbaecker Jonathan Beesley Julian Adlard Bjarni A Agnarsson Irene L Andrulis Banu K Arun Laure Barjhoux Muriel Belotti Javier Benitez Andreas Berger Anders Bojesen Bernardo Bonanni Carole Brewer Trinidad Caldes Maria A Caligo Ian Campbell Salina B Chan Kathleen B M Claes David E Cohn Jackie Cook Mary B Daly Francesca Damiola Rosemarie Davidson Antoine de Pauw Capucine Delnatte Orland Diez Susan M Domchek Martine Dumont Katarzyna Durda Bernd Dworniczak Douglas F Easton Diana Eccles Christina Edwinsdotter Ardnor Ros Eeles Bent Ejlertsen Steve Ellis D Gareth Evans Lidia Feliubadalo Florentia Fostira William D Foulkes Eitan Friedman Debra Frost Pragna Gaddam Patricia A Ganz Judy Garber Vanesa Garcia-Barberan Marion Gauthier-Villars Andrea Gehrig Anne-Marie Gerdes Sophie Giraud Andrew K Godwin David E Goldgar Christopher R Hake Thomas V O Hansen Sue Healey Shirley Hodgson Frans B L Hogervorst Claude Houdayer Peter J Hulick Evgeny N Imyanitov Claudine Isaacs Louise Izatt Angel Izquierdo Lauren Jacobs Anna Jakubowska Ramunas Janavicius Katarzyna Jaworska-Bieniek Uffe Birk Jensen Esther M John Joseph Vijai Beth Y Karlan Karin Kast KConFab Investigators Sofia Khan Ava Kwong Yael Laitman Jenny Lester Fabienne Lesueur Annelie Liljegren Jan Lubinski Phuong L Mai Siranoush Manoukian Sylvie Mazoyer Alfons Meindl Arjen R Mensenkamp Marco Montagna Katherine L Nathanson Susan L Neuhausen Heli Nevanlinna Dieter Niederacher Edith Olah Olufunmilayo I Olopade Kai-Ren Ong Ana Osorio Sue Kyung Park Ylva Paulsson-Karlsson Inge Sokilde Pedersen Bernard Peissel Paolo Peterlongo Georg Pfeiler Catherine M Phelan Marion Piedmonte Bruce Poppe Miquel Angel Pujana Paolo Radice Gad Rennert Gustavo C Rodriguez Matti A Rookus Eric A Ross Rita Katharina Schmutzler Jacques Simard Christian F Singer Thomas P Slavin Penny Soucy Melissa Southey Doris Steinemann Dominique Stoppa-Lyonnet Grzegorz Sukiennicki Christian Sutter Csilla I Szabo Muy-Kheng Tea Manuel R Teixeira Soo-Hwang Teo Mary Beth Terry Mads Thomassen Maria Grazia Tibiletti Laima Tihomirova Silvia Tognazzo Elizabeth J van Rensburg Liliana Varesco Raymonda Varon-Mateeva Athanassios Vratimos Jeffrey N Weitzel Lesley McGuffog Judy Kirk Amanda Ewart Toland Ute Hamann Noralane Lindor Susan J Ramus Mark H Greene Fergus J Couch Kenneth Offit Paul D P Pharoah Georgia Chenevix-Trench Antonis C Antoniou |
| author_facet | Elena Vigorito Karoline B Kuchenbaecker Jonathan Beesley Julian Adlard Bjarni A Agnarsson Irene L Andrulis Banu K Arun Laure Barjhoux Muriel Belotti Javier Benitez Andreas Berger Anders Bojesen Bernardo Bonanni Carole Brewer Trinidad Caldes Maria A Caligo Ian Campbell Salina B Chan Kathleen B M Claes David E Cohn Jackie Cook Mary B Daly Francesca Damiola Rosemarie Davidson Antoine de Pauw Capucine Delnatte Orland Diez Susan M Domchek Martine Dumont Katarzyna Durda Bernd Dworniczak Douglas F Easton Diana Eccles Christina Edwinsdotter Ardnor Ros Eeles Bent Ejlertsen Steve Ellis D Gareth Evans Lidia Feliubadalo Florentia Fostira William D Foulkes Eitan Friedman Debra Frost Pragna Gaddam Patricia A Ganz Judy Garber Vanesa Garcia-Barberan Marion Gauthier-Villars Andrea Gehrig Anne-Marie Gerdes Sophie Giraud Andrew K Godwin David E Goldgar Christopher R Hake Thomas V O Hansen Sue Healey Shirley Hodgson Frans B L Hogervorst Claude Houdayer Peter J Hulick Evgeny N Imyanitov Claudine Isaacs Louise Izatt Angel Izquierdo Lauren Jacobs Anna Jakubowska Ramunas Janavicius Katarzyna Jaworska-Bieniek Uffe Birk Jensen Esther M John Joseph Vijai Beth Y Karlan Karin Kast KConFab Investigators Sofia Khan Ava Kwong Yael Laitman Jenny Lester Fabienne Lesueur Annelie Liljegren Jan Lubinski Phuong L Mai Siranoush Manoukian Sylvie Mazoyer Alfons Meindl Arjen R Mensenkamp Marco Montagna Katherine L Nathanson Susan L Neuhausen Heli Nevanlinna Dieter Niederacher Edith Olah Olufunmilayo I Olopade Kai-Ren Ong Ana Osorio Sue Kyung Park Ylva Paulsson-Karlsson Inge Sokilde Pedersen Bernard Peissel Paolo Peterlongo Georg Pfeiler Catherine M Phelan Marion Piedmonte Bruce Poppe Miquel Angel Pujana Paolo Radice Gad Rennert Gustavo C Rodriguez Matti A Rookus Eric A Ross Rita Katharina Schmutzler Jacques Simard Christian F Singer Thomas P Slavin Penny Soucy Melissa Southey Doris Steinemann Dominique Stoppa-Lyonnet Grzegorz Sukiennicki Christian Sutter Csilla I Szabo Muy-Kheng Tea Manuel R Teixeira Soo-Hwang Teo Mary Beth Terry Mads Thomassen Maria Grazia Tibiletti Laima Tihomirova Silvia Tognazzo Elizabeth J van Rensburg Liliana Varesco Raymonda Varon-Mateeva Athanassios Vratimos Jeffrey N Weitzel Lesley McGuffog Judy Kirk Amanda Ewart Toland Ute Hamann Noralane Lindor Susan J Ramus Mark H Greene Fergus J Couch Kenneth Offit Paul D P Pharoah Georgia Chenevix-Trench Antonis C Antoniou |
| author_sort | Elena Vigorito |
| collection | DOAJ |
| description | Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95%CI: 0.68 to 0.79, p-value 2× 10-16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population. |
| format | Article |
| id | doaj-art-3218667a15f94b26bb725ac2e8a2bbda |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-3218667a15f94b26bb725ac2e8a2bbda2025-08-20T02:31:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01117e015880110.1371/journal.pone.0158801Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.Elena VigoritoKaroline B KuchenbaeckerJonathan BeesleyJulian AdlardBjarni A AgnarssonIrene L AndrulisBanu K ArunLaure BarjhouxMuriel BelottiJavier BenitezAndreas BergerAnders BojesenBernardo BonanniCarole BrewerTrinidad CaldesMaria A CaligoIan CampbellSalina B ChanKathleen B M ClaesDavid E CohnJackie CookMary B DalyFrancesca DamiolaRosemarie DavidsonAntoine de PauwCapucine DelnatteOrland DiezSusan M DomchekMartine DumontKatarzyna DurdaBernd DworniczakDouglas F EastonDiana EcclesChristina Edwinsdotter ArdnorRos EelesBent EjlertsenSteve EllisD Gareth EvansLidia FeliubadaloFlorentia FostiraWilliam D FoulkesEitan FriedmanDebra FrostPragna GaddamPatricia A GanzJudy GarberVanesa Garcia-BarberanMarion Gauthier-VillarsAndrea GehrigAnne-Marie GerdesSophie GiraudAndrew K GodwinDavid E GoldgarChristopher R HakeThomas V O HansenSue HealeyShirley HodgsonFrans B L HogervorstClaude HoudayerPeter J HulickEvgeny N ImyanitovClaudine IsaacsLouise IzattAngel IzquierdoLauren JacobsAnna JakubowskaRamunas JanaviciusKatarzyna Jaworska-BieniekUffe Birk JensenEsther M JohnJoseph VijaiBeth Y KarlanKarin KastKConFab InvestigatorsSofia KhanAva KwongYael LaitmanJenny LesterFabienne LesueurAnnelie LiljegrenJan LubinskiPhuong L MaiSiranoush ManoukianSylvie MazoyerAlfons MeindlArjen R MensenkampMarco MontagnaKatherine L NathansonSusan L NeuhausenHeli NevanlinnaDieter NiederacherEdith OlahOlufunmilayo I OlopadeKai-Ren OngAna OsorioSue Kyung ParkYlva Paulsson-KarlssonInge Sokilde PedersenBernard PeisselPaolo PeterlongoGeorg PfeilerCatherine M PhelanMarion PiedmonteBruce PoppeMiquel Angel PujanaPaolo RadiceGad RennertGustavo C RodriguezMatti A RookusEric A RossRita Katharina SchmutzlerJacques SimardChristian F SingerThomas P SlavinPenny SoucyMelissa SoutheyDoris SteinemannDominique Stoppa-LyonnetGrzegorz SukiennickiChristian SutterCsilla I SzaboMuy-Kheng TeaManuel R TeixeiraSoo-Hwang TeoMary Beth TerryMads ThomassenMaria Grazia TibilettiLaima TihomirovaSilvia TognazzoElizabeth J van RensburgLiliana VarescoRaymonda Varon-MateevaAthanassios VratimosJeffrey N WeitzelLesley McGuffogJudy KirkAmanda Ewart TolandUte HamannNoralane LindorSusan J RamusMark H GreeneFergus J CouchKenneth OffitPaul D P PharoahGeorgia Chenevix-TrenchAntonis C AntoniouPopulation-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95%CI: 0.68 to 0.79, p-value 2× 10-16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0158801&type=printable |
| spellingShingle | Elena Vigorito Karoline B Kuchenbaecker Jonathan Beesley Julian Adlard Bjarni A Agnarsson Irene L Andrulis Banu K Arun Laure Barjhoux Muriel Belotti Javier Benitez Andreas Berger Anders Bojesen Bernardo Bonanni Carole Brewer Trinidad Caldes Maria A Caligo Ian Campbell Salina B Chan Kathleen B M Claes David E Cohn Jackie Cook Mary B Daly Francesca Damiola Rosemarie Davidson Antoine de Pauw Capucine Delnatte Orland Diez Susan M Domchek Martine Dumont Katarzyna Durda Bernd Dworniczak Douglas F Easton Diana Eccles Christina Edwinsdotter Ardnor Ros Eeles Bent Ejlertsen Steve Ellis D Gareth Evans Lidia Feliubadalo Florentia Fostira William D Foulkes Eitan Friedman Debra Frost Pragna Gaddam Patricia A Ganz Judy Garber Vanesa Garcia-Barberan Marion Gauthier-Villars Andrea Gehrig Anne-Marie Gerdes Sophie Giraud Andrew K Godwin David E Goldgar Christopher R Hake Thomas V O Hansen Sue Healey Shirley Hodgson Frans B L Hogervorst Claude Houdayer Peter J Hulick Evgeny N Imyanitov Claudine Isaacs Louise Izatt Angel Izquierdo Lauren Jacobs Anna Jakubowska Ramunas Janavicius Katarzyna Jaworska-Bieniek Uffe Birk Jensen Esther M John Joseph Vijai Beth Y Karlan Karin Kast KConFab Investigators Sofia Khan Ava Kwong Yael Laitman Jenny Lester Fabienne Lesueur Annelie Liljegren Jan Lubinski Phuong L Mai Siranoush Manoukian Sylvie Mazoyer Alfons Meindl Arjen R Mensenkamp Marco Montagna Katherine L Nathanson Susan L Neuhausen Heli Nevanlinna Dieter Niederacher Edith Olah Olufunmilayo I Olopade Kai-Ren Ong Ana Osorio Sue Kyung Park Ylva Paulsson-Karlsson Inge Sokilde Pedersen Bernard Peissel Paolo Peterlongo Georg Pfeiler Catherine M Phelan Marion Piedmonte Bruce Poppe Miquel Angel Pujana Paolo Radice Gad Rennert Gustavo C Rodriguez Matti A Rookus Eric A Ross Rita Katharina Schmutzler Jacques Simard Christian F Singer Thomas P Slavin Penny Soucy Melissa Southey Doris Steinemann Dominique Stoppa-Lyonnet Grzegorz Sukiennicki Christian Sutter Csilla I Szabo Muy-Kheng Tea Manuel R Teixeira Soo-Hwang Teo Mary Beth Terry Mads Thomassen Maria Grazia Tibiletti Laima Tihomirova Silvia Tognazzo Elizabeth J van Rensburg Liliana Varesco Raymonda Varon-Mateeva Athanassios Vratimos Jeffrey N Weitzel Lesley McGuffog Judy Kirk Amanda Ewart Toland Ute Hamann Noralane Lindor Susan J Ramus Mark H Greene Fergus J Couch Kenneth Offit Paul D P Pharoah Georgia Chenevix-Trench Antonis C Antoniou Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers. PLoS ONE |
| title | Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers. |
| title_full | Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers. |
| title_fullStr | Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers. |
| title_full_unstemmed | Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers. |
| title_short | Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers. |
| title_sort | fine scale mapping at 9p22 2 identifies candidate causal variants that modify ovarian cancer risk in brca1 and brca2 mutation carriers |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0158801&type=printable |
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finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT olufunmilayoiolopade finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT kairenong finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT anaosorio finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT suekyungpark finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT ylvapaulssonkarlsson finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT ingesokildepedersen finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT bernardpeissel finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT paolopeterlongo finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT georgpfeiler finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT catherinemphelan finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT marionpiedmonte finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT brucepoppe finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT miquelangelpujana finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT paoloradice finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT gadrennert finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT gustavocrodriguez finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT mattiarookus finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT ericaross finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT ritakatharinaschmutzler finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT jacquessimard finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT christianfsinger finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT thomaspslavin finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT pennysoucy finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT melissasouthey finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT dorissteinemann finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT dominiquestoppalyonnet finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT grzegorzsukiennicki finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT christiansutter 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finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT laimatihomirova finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT silviatognazzo finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT elizabethjvanrensburg finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT lilianavaresco finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT raymondavaronmateeva finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT athanassiosvratimos finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT jeffreynweitzel finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT lesleymcguffog finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT judykirk finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT amandaewarttoland finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT utehamann finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT noralanelindor finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT susanjramus finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT markhgreene finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT fergusjcouch finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT kennethoffit finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT pauldppharoah finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT georgiachenevixtrench finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers AT antoniscantoniou finescalemappingat9p222identifiescandidatecausalvariantsthatmodifyovariancancerriskinbrca1andbrca2mutationcarriers |