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@article{Lu:2018:10.1158/0008-5472.CAN-18-0951,
author = {Lu, Y and Beeghly-Fadiel, A and Wu, L and Guo, X and Li, B and Schildkraut, JM and Im, HK and Chen, YA and Permuth, JB and Reid, BM and Teer, JK and Moysich, KB and Andrulis, IL and Anton-Culver, H and Arun, BK and Bandera, EV and Barkardottir, RB and Barnes, DR and Benitez, J and Bjørge, L and Brenton, J and Butzow, R and Caldes, T and Caligo, MA and Campbell, IG and Chang-Claude, J and Claes, KBM and Couch, FJ and Cramer, DW and Daly, MB and DeFazio, A and Dennis, J and Díez, O and Domchek, SM and Dork, T and Easton, DF and Eccles, DM and Fasching, PA and Fortner, RT and Fountzilas, G and Friedman, E and Ganz, PA and Garber, J and Giles, GG and Godwin, AK and Goldgar, DE and Goodman, MT and Greene, MH and Gronwald, J and Hamann, U and Heitz, F and Hildebrandt, MAT and Høgdall, CK and Hollestelle, A and Hulick, PJ and Huntsman, DG and Imyanitov, EN and Isaacs, C and Jakubowska, A and James, P and Karlan, BY and Kelemen, LE and Kiemeney, LA and Kjaer, SK and Kwong, A and Le, ND and Les},
doi = {10.1158/0008-5472.CAN-18-0951},
journal = {Cancer Research},
pages = {5419--5430},
title = {A transcriptome-wide association study among 97,898 women to identify candidate susceptibility genes for epithelial ovarian cancer risk},
url = {http://dx.doi.org/10.1158/0008-5472.CAN-18-0951},
volume = {78},
year = {2018}
}

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TY  - JOUR
AB  - Large-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in non-coding regions, and causal genes underlying these associations remain largely unknown. Here we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci. We used RNA sequencing data (68 normal ovarian-tissue samples from 68 individuals and 6,124 cross-tissue samples from 369 individuals) and high-density genotyping data from European descendants of the Genotype-Tissue Expression (GTEx V6) project to build ovarian and cross-tissue models of genetically regulated expression using elastic net methods. We evaluated 17,121 genes for their cis-predicted gene expression in relation to EOC risk using summary statistics data from GWAS of 97,898 women, including 29,396 EOC cases. With a Bonferroni-corrected significance level of P<2.2×10-6, we identified 35 genes including FZD4 at 11q14.2 (Z=5.08, P=3.83×10-7, the cross-tissue model; 1 Mb away from any GWAS-identified EOC risk variant), a potential novel locus for EOC risk. All other 34 significantly-associated genes were located within 1 Mb of known GWAS-identified loci, including 23 genes at 6 loci not previously linked to EOC risk. Upon conditioning on nearby known EOC GWAS-identified variants, the associations for 31 genes disappeared and 3 genes remained (P<1.47 x 10-3). These data identify one novel locus (FZD4) and 34 genes at 13 known EOC risk loci associated with EOC risk, providing new insights into EOC carcinogenesis.
AU  - Lu,Y
AU  - Beeghly-Fadiel,A
AU  - Wu,L
AU  - Guo,X
AU  - Li,B
AU  - Schildkraut,JM
AU  - Im,HK
AU  - Chen,YA
AU  - Permuth,JB
AU  - Reid,BM
AU  - Teer,JK
AU  - Moysich,KB
AU  - Andrulis,IL
AU  - Anton-Culver,H
AU  - Arun,BK
AU  - Bandera,EV
AU  - Barkardottir,RB
AU  - Barnes,DR
AU  - Benitez,J
AU  - Bjørge,L
AU  - Brenton,J
AU  - Butzow,R
AU  - Caldes,T
AU  - Caligo,MA
AU  - Campbell,IG
AU  - Chang-Claude,J
AU  - Claes,KBM
AU  - Couch,FJ
AU  - Cramer,DW
AU  - Daly,MB
AU  - DeFazio,A
AU  - Dennis,J
AU  - Díez,O
AU  - Domchek,SM
AU  - Dork,T
AU  - Easton,DF
AU  - Eccles,DM
AU  - Fasching,PA
AU  - Fortner,RT
AU  - Fountzilas,G
AU  - Friedman,E
AU  - Ganz,PA
AU  - Garber,J
AU  - Giles,GG
AU  - Godwin,AK
AU  - Goldgar,DE
AU  - Goodman,MT
AU  - Greene,MH
AU  - Gronwald,J
AU  - Hamann,U
AU  - Heitz,F
AU  - Hildebrandt,MAT
AU  - Høgdall,CK
AU  - Hollestelle,A
AU  - Hulick,PJ
AU  - Huntsman,DG
AU  - Imyanitov,EN
AU  - Isaacs,C
AU  - Jakubowska,A
AU  - James,P
AU  - Karlan,BY
AU  - Kelemen,LE
AU  - Kiemeney,LA
AU  - Kjaer,SK
AU  - Kwong,A
AU  - Le,ND
AU  - Leslie,G
AU  - Lesueur,F
AU  - Levine,DA
AU  - Mattiello,A
AU  - May,T
AU  - McGuffog,L
AU  - McNeish,IA
AU  - Merritt,MA
AU  - Modugno,F
AU  - Montagna,M
AU  - Neuhausen,SL
AU  - Nevanlinna,H
AU  - Cilius,Nielsen FC
AU  - Nikitina-Zake,L
AU  - Nussbaum,RL
AU  - Offit,K
AU  - Olah,E
AU  - Olopade,OI
AU  - Olson,SH
AU  - Olsson,H
AU  - Osorio,A
AU  - Park,SK
AU  - Parsons,MT
AU  - Peeters,PHM
AU  - Pejovic,T
AU  - Peterlongo,P
AU  - Phelan,CM
AU  - Pujana,MA
AU  - Ramus,SJ
AU  - Rennert,G
AU  - Risch,H
AU  - Rodriguez,GC
AU  - Rodríguez-Antona,C
AU  - Romieu,I
AU  - Rookus,MA
AU  - Rossing,MA
AU  - Rzepecka,IK
AU  - Sandler,DP
AU  - Schmutzler,RK
AU  - Setiawan,VW
AU  - Sharma,P
AU  - Sieh,W
AU  - Simard,J
AU  - Singer,CF
AU  - Song,H
AU  - Southey,MC
AU  - Spurdle,AB
AU  - Sutphen,R
AU  - Swerdlow,AJ
AU  - Teixeira,MR
AU  - Teo,SH
AU  - Thomassen,M
AU  - Tischkowitz,M
AU  - Toland,AE
AU  - Trichopoulou,A
AU  - Tung,N
AU  - Tworoger,SS
AU  - van,Rensburg EJ
AU  - Vanderstichele,A
AU  - Vega,A
AU  - Velez,Edwards D
AU  - Webb,PM
AU  - Weitzel,JN
AU  - Wentzensen,N
AU  - White,E
AU  - Wolk,A
AU  - Wu,AH
AU  - Yannoukakos,D
AU  - Zorn,KK
AU  - Gayther,SA
AU  - Antoniou,AC
AU  - Berchuck,A
AU  - Goode,EL
AU  - Chenevix-Trench,G
AU  - Sellers,TA
AU  - Pharoah,PDP
AU  - Zheng,W
AU  - Long,J
DO  - 10.1158/0008-5472.CAN-18-0951
EP  - 5430
PY  - 2018///
SN  - 1538-7445
SP  - 5419
TI  - A transcriptome-wide association study among 97,898 women to identify candidate susceptibility genes for epithelial ovarian cancer risk
T2  - Cancer Research
UR  - http://dx.doi.org/10.1158/0008-5472.CAN-18-0951
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30054336
UR  - https://cancerres.aacrjournals.org/content/78/18/5419
UR  - http://hdl.handle.net/10044/1/61623
VL  - 78
ER  -

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