BibTex format
@article{Barnes:2024:10.1101/2024.02.29.24303243,
author = {Barnes, DR and Tyrer, JP and Dennis, J and Leslie, G and Bolla, MK and Lush, M and Aeilts, AM and Aittomäki, K and Andrieu, N and Andrulis, IL and Anton-Culver, H and Arason, A and Arun, BK and Balmaña, J and Bandera, EV and Barkardottir, RB and Berger, LPV and de, Gonzalez AB and Berthet, P and Biakowska, K and Bjørge, L and Blanco, AM and Blok, MJ and Bobolis, KA and Bogdanova, NV and Brenton, JD and Butz, H and Buys, SS and Caligo, MA and Campbell, I and Castillo, C and Claes, KBM and GEMO, Study Collaborators and EMBRACE, Collaborators and Colonna, SV and Cook, LS and Daly, MB and Dansonka-Mieszkowska, A and de, la Hoya M and deFazio, A and DePersia, A and Ding, YC and Domchek, SM and Dörk, T and Einbeigi, Z and Engel, C and Evans, DG and Foretova, L and Fortner, RT and Fostira, F and Foti, MC and Friedman, E and Frone, MN and Ganz, PA and Gentry-Maharaj, A and Glendon, G and Godwin, AK and González-Neira, A and Greene, MH and Gronwald, J and Guerrieri-Gonzaga, A and Hamann, U and },
doi = {10.1101/2024.02.29.24303243},
journal = {medRxiv},
title = {Large-scale genome-wide association study of 398,238 women unveils seven novel loci associated with high-grade serous epithelial ovarian cancer risk.},
url = {http://dx.doi.org/10.1101/2024.02.29.24303243},
year = {2024}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - BACKGROUND: Nineteen genomic regions have been associated with high-grade serous ovarian cancer (HGSOC). We used data from the Ovarian Cancer Association Consortium (OCAC), Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA), UK Biobank (UKBB), and FinnGen to identify novel HGSOC susceptibility loci and develop polygenic scores (PGS). METHODS: We analyzed >22 million variants for 398,238 women. Associations were assessed separately by consortium and meta-analysed. OCAC and CIMBA data were used to develop PGS which were trained on FinnGen data and validated in UKBB and BioBank Japan. RESULTS: Eight novel variants were associated with HGSOC risk. An interesting discovery biologically was finding that TP53 3'-UTR SNP rs78378222 was associated with HGSOC (per T allele relative risk (RR)=1.44, 95%CI:1.28-1.62, P=1.76×10-9). The optimal PGS included 64,518 variants and was associated with an odds ratio of 1.46 (95%CI:1.37-1.54) per standard deviation in the UKBB validation (AUROC curve=0.61, 95%CI:0.59-0.62). CONCLUSIONS: This study represents the largest GWAS for HGSOC to date. The results highlight that improvements in imputation reference panels and increased sample sizes can identify HGSOC associated variants that previously went undetected, resulting in improved PGS. The use of updated PGS in cancer risk prediction algorithms will then improve personalized risk prediction for HGSOC.
AU - Barnes,DR
AU - Tyrer,JP
AU - Dennis,J
AU - Leslie,G
AU - Bolla,MK
AU - Lush,M
AU - Aeilts,AM
AU - Aittomäki,K
AU - Andrieu,N
AU - Andrulis,IL
AU - Anton-Culver,H
AU - Arason,A
AU - Arun,BK
AU - Balmaña,J
AU - Bandera,EV
AU - Barkardottir,RB
AU - Berger,LPV
AU - de,Gonzalez AB
AU - Berthet,P
AU - Biakowska,K
AU - Bjørge,L
AU - Blanco,AM
AU - Blok,MJ
AU - Bobolis,KA
AU - Bogdanova,NV
AU - Brenton,JD
AU - Butz,H
AU - Buys,SS
AU - Caligo,MA
AU - Campbell,I
AU - Castillo,C
AU - Claes,KBM
AU - GEMO,Study Collaborators
AU - EMBRACE,Collaborators
AU - Colonna,SV
AU - Cook,LS
AU - Daly,MB
AU - Dansonka-Mieszkowska,A
AU - de,la Hoya M
AU - deFazio,A
AU - DePersia,A
AU - Ding,YC
AU - Domchek,SM
AU - Dörk,T
AU - Einbeigi,Z
AU - Engel,C
AU - Evans,DG
AU - Foretova,L
AU - Fortner,RT
AU - Fostira,F
AU - Foti,MC
AU - Friedman,E
AU - Frone,MN
AU - Ganz,PA
AU - Gentry-Maharaj,A
AU - Glendon,G
AU - Godwin,AK
AU - González-Neira,A
AU - Greene,MH
AU - Gronwald,J
AU - Guerrieri-Gonzaga,A
AU - Hamann,U
AU - Hansen,TVO
AU - Harris,HR
AU - Hauke,J
AU - Heitz,F
AU - Hogervorst,FBL
AU - Hooning,MJ
AU - Hopper,JL
AU - Huff,CD
AU - Huntsman,DG
AU - Imyanitov,EN
AU - kConFab,Investigators
AU - Izatt,L
AU - Jakubowska,A
AU - James,PA
AU - Janavicius,R
AU - John,EM
AU - Kar,S
AU - Karlan,BY
AU - Kennedy,CJ
AU - Kiemeney,LALM
AU - Konstantopoulou,I
AU - Kupryjanczyk,J
AU - Laitman,Y
AU - Lavie,O
AU - Lawrenson,K
AU - Lester,J
AU - Lesueur,F
AU - Lopez-Pleguezuelos,C
AU - Mai,PL
AU - Manoukian,S
AU - May,T
AU - McNeish,IA
AU - Menon,U
AU - Milne,RL
AU - Modugno,F
AU - Mongiovi,JM
AU - Montagna,M
AU - Moysich,KB
AU - Neuhausen,SL
AU - Nielsen,FC
AU - Noguès,C
AU - Oláh,E
AU - Olopade,OI
AU - Osorio,A
AU - Papi,L
AU - Pathak,H
AU - Pearce,CL
AU - Pedersen,IS
AU - Peixoto,A
AU - Pejovic,T
AU - Peng,P-C
AU - Peshkin,BN
AU - Peterlongo,P
AU - Powell,CB
AU - Prokofyeva,D
AU - Pujana,MA
AU - Radice,P
AU - Rashid,MU
AU - Rennert,G
AU - Richenberg,G
AU - Sandler,DP
AU - Sasamoto,N
AU - Setiawan,VW
AU - Sharma,P
AU - Sieh,W
AU - Singer,CF
AU - Snape,K
AU - Sokolenko,AP
AU - Soucy,P
AU - Southey,MC
AU - Stoppa-Lyonnet,D
AU - Sutphen,R
AU - Sutter,C
AU - Teixeira,MR
AU - Terry,KL
AU - Thomsen,LCV
AU - Tischkowitz,M
AU - Toland,AE
AU - Van,Gorp T
AU - Vega,A
AU - Velez,Edwards DR
AU - Webb,PM
AU - Weitzel,JN
AU - Wentzensen,N
AU - Whittemore,AS
AU - Winham,SJ
AU - Wu,AH
AU - Yadav,S
AU - Yu,Y
AU - Ziogas,A
AU - Berchuck,A
AU - Couch,FJ
AU - Goode,EL
AU - Goodman,MT
AU - Monteiro,AN
AU - Offit,K
AU - Ramus,SJ
AU - Risch,HA
AU - Schildkraut,JM
AU - Thomassen,M
AU - Simard,J
AU - Easton,DF
AU - Jones,MR
AU - Chenevix-Trench,G
AU - Gayther,SA
AU - Antoniou,AC
AU - Pharoa
DO - 10.1101/2024.02.29.24303243
PY - 2024///
TI - Large-scale genome-wide association study of 398,238 women unveils seven novel loci associated with high-grade serous epithelial ovarian cancer risk.
T2 - medRxiv
UR - http://dx.doi.org/10.1101/2024.02.29.24303243
UR - https://www.ncbi.nlm.nih.gov/pubmed/38496424
ER -