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@ARTICLE{Lu:142083,
author = {Y. Lu and A. Beeghly-Fadiel and L. Wu and X. Guo and B. Li
and J. M. Schildkraut and H. K. Im and Y. A. Chen and J. B.
Permuth and B. M. Reid and J. K. Teer and K. B. Moysich and
I. L. Andrulis and H. Anton-Culver and B. K. Arun and E. V.
Bandera and R. B. Barkardottir and D. R. Barnes and J.
Benitez and L. Bjorge and J. Brenton and R. Butzow and T.
Caldes and M. A. Caligo and I. Campbell and J.
Chang-Claude$^*$ and K. B. M. Claes and F. J. Couch and D.
W. Cramer and M. B. Daly and A. deFazio and J. Dennis and O.
Diez and S. M. Domchek and T. Dörk and D. F. Easton and D.
M. Eccles and P. A. Fasching and R. Turzanski-Fortner$^*$
and G. Fountzilas and E. Friedman and P. A. Ganz and J.
Garber and G. G. Giles and A. K. Godwin and D. E. Goldgar
and M. T. Goodman and M. H. Greene and J. Gronwald and U.
Hamann$^*$ and F. Heitz and M. A. T. Hildebrandt and C. K.
Høgdall and A. Hollestelle and P. J. Hulick and D. G.
Huntsman and E. N. Imyanitov and C. Isaacs and A. Jakubowska
and P. James and B. Y. Karlan and L. E. Kelemen and L. A.
Kiemeney and S. K. Kjaer and A. Kwong and N. D. Le and G.
Leslie and F. Lesueur and D. A. Levine and A. Mattiello and
T. May and L. McGuffog and I. A. McNeish and M. A. Merritt
and F. Modugno and M. Montagna and S. L. Neuhausen and H.
Nevanlinna and F. C. Nielsen and L. Nikitina-Zake and R. L.
Nussbaum and K. Offit and E. Olah and O. I. Olopade and S.
H. Olson and H. Olsson and A. Osorio and S. K. Park and M.
T. Parsons and P. H. M. Peeters and T. Pejovic and P.
Peterlongo and C. M. Phelan and M. A. Pujana and S. J. Ramus
and G. Rennert and H. Risch and G. C. Rodriguez and C.
Rodríguez-Antona and I. Romieu and M. A. Rookus and M. A.
Rossing and I. K. Rzepecka and D. P. Sandler and R. K.
Schmutzler and V. W. Setiawan and P. Sharma and W. Sieh and
J. Simard and C. F. Singer and H. Song and M. C. Southey and
A. B. Spurdle and R. Sutphen and A. J. Swerdlow and M. R.
Teixeira and S. H. Teo and M. Thomassen and M. Tischkowitz
and A. E. Toland and A. Trichopoulou and N. Tung and S. S.
Tworoger and E. J. van Rensburg and A. Vanderstichele and A.
Vega and D. V. Edwards and P. M. Webb and J. N. Weitzel and
N. Wentzensen and E. White and A. Wolk and A. H. Wu and D.
Yannoukakos and K. K. Zorn and S. A. Gayther and A. C.
Antoniou and A. Berchuck and E. L. Goode and G.
Chenevix-Trench and T. A. Sellers and P. D. P. Pharoah and
W. Zheng and J. Long},
title = {{A} {T}ranscriptome-{W}ide {A}ssociation {S}tudy {A}mong
97,898 {W}omen to {I}dentify {C}andidate {S}usceptibility
{G}enes for {E}pithelial {O}varian {C}ancer {R}isk.},
journal = {Cancer research},
volume = {78},
number = {18},
issn = {1538-7445},
address = {Philadelphia, Pa.},
publisher = {AACR},
reportid = {DKFZ-2018-02313},
pages = {5419 - 5430},
year = {2018},
abstract = {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 noncoding
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 three genes remained (P < 1.47 ×
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.Significance:
Transcriptomic analysis of a large cohort confirms earlier
GWAS loci and reveals FZD4 as a novel locus associated with
EOC risk. Cancer Res; 78(18); 5419-30. ©2018 AACR.},
cin = {C020 / B072},
ddc = {610},
cid = {I:(DE-He78)C020-20160331 / I:(DE-He78)B072-20160331},
pnm = {319H - Addenda (POF3-319H)},
pid = {G:(DE-HGF)POF3-319H},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30054336},
pmc = {pmc:PMC6139053},
doi = {10.1158/0008-5472.CAN-18-0951},
url = {https://inrepo02.dkfz.de/record/142083},
}