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@ARTICLE{Dareng:290096,
author = {E. O. Dareng and S. G. Coetzee and J. P. Tyrer and P.-C.
Peng and W. Rosenow and S. Chen and B. D. Davis and F. S.
Dezem and J.-H. Seo and R. Nameki and A. L. Reyes and K. K.
H. Aben and H. Anton-Culver and N. N. Antonenkova and G.
Aravantinos and E. V. Bandera and L. E. Beane Freeman and M.
W. Beckmann and A. Beeghly-Fadiel and J. Benitez and M. Q.
Bernardini and L. Bjorge and A. Black and N. V. Bogdanova
and K. L. Bolton and J. D. Brenton and A. Budzilowska and R.
Butzow and H. Cai and I. Campbell and R. Cannioto and J.
Chang-Claude$^*$ and S. J. Chanock and K. Chen and G.
Chenevix-Trench and Y.-E. Chiew and L. S. Cook and A.
DeFazio and J. Dennis and J. A. Doherty and T. Dörk and A.
du Bois and M. Dürst and D. M. Eccles and G. Ene and P. A.
Fasching and J. M. Flanagan and R. T. Fortner$^*$ and F.
Fostira and A. Gentry-Maharaj and G. G. Giles and M. T.
Goodman and J. Gronwald and C. A. Haiman and N. Håkansson
and F. Heitz and M. A. T. Hildebrandt and E. Høgdall and C.
K. Høgdall and R.-Y. Huang and A. Jensen and M. E. Jones
and D. Kang and B. Y. Karlan and A. N. Karnezis and L. E.
Kelemen and C. J. Kennedy and E. K. Khusnutdinova and L. A.
Kiemeney and S. K. Kjaer and J. Kupryjanczyk and M. Labrie
and D. Lambrechts and M. C. Larson and N. D. Le and J.
Lester and L. Li and J. Lubiński and M. Lush and J. R.
Marks and K. Matsuo and T. May and J. R. McLaughlin and I.
A. McNeish and U. Menon and S. Missmer and F. Modugno and M.
Moffitt and A. N. Monteiro and K. B. Moysich and S. A. Narod
and T. Nguyen-Dumont and K. Odunsi and H. Olsson and N. C.
Onland-Moret and S. K. Park and T. Pejovic and J. B. Permuth
and A. Piskorz and D. Prokofyeva and M. J. Riggan and H. A.
Risch and C. Rodríguez-Antona and M. A. Rossing and D. P.
Sandler and V. W. Setiawan and K. Shan and H. Song and M. C.
Southey and H. Steed and R. Sutphen and A. J. Swerdlow and
S. H. Teo and K. L. Terry and P. J. Thompson and L. C.
Vestrheim Thomsen and L. Titus and B. Trabert and R. Travis
and S. S. Tworoger and E. Valen and E. Van Nieuwenhuysen and
D. V. Edwards and R. A. Vierkant and P. M. Webb and C. R.
Weinberg and R. M. Weise and N. Wentzensen and E. White and
S. J. Winham and A. Wolk and Y.-L. Woo and A. H. Wu and L.
Yan and D. Yannoukakos and N. Zeinomar and W. Zheng and A.
Ziogas and A. Berchuck and E. L. Goode and D. G. Huntsman
and C. L. Pearce and S. J. Ramus and T. A. Sellers and M. L.
Freedman and K. Lawrenson and J. M. Schildkraut and D.
Hazelett and J. T. Plummer and S. Kar and M. R. Jones and P.
D. P. Pharoah and S. A. Gayther},
collaboration = {A. Group and O. S. Group and O. C. A. Consortium},
title = {{I}ntegrative multi-omics analyses to identify the genetic
and functional mechanisms underlying ovarian cancer risk
regions.},
journal = {The American journal of human genetics},
volume = {111},
number = {6},
issn = {0002-9297},
address = {New York, NY},
publisher = {Elsevier},
reportid = {DKFZ-2024-00995},
pages = {1061-1083},
year = {2024},
note = {2024 Jun 6;111(6):1061-1083},
abstract = {To identify credible causal risk variants (CCVs) associated
with different histotypes of epithelial ovarian cancer
(EOC), we performed genome-wide association analysis for
470,825 genotyped and 10,163,797 imputed SNPs in 25,981 EOC
cases and 105,724 controls of European origin. We identified
five histotype-specific EOC risk regions (p value <5 ×
10-8) and confirmed previously reported associations for 27
risk regions. Conditional analyses identified an additional
11 signals independent of the primary signal at six risk
regions (p value <10-5). Fine mapping identified 4,008 CCVs
in these regions, of which 1,452 CCVs were located in
ovarian cancer-related chromatin marks with significant
enrichment in active enhancers, active promoters, and active
regions for CCVs from each EOC histotype. Transcriptome-wide
association and colocalization analyses across histotypes
using tissue-specific and cross-tissue datasets identified
86 candidate susceptibility genes in known EOC risk regions
and 32 genes in 23 additional genomic regions that may
represent novel EOC risk loci (false discovery rate <0.05).
Finally, by integrating genome-wide HiChIP interactome
analysis with transcriptome-wide association study (TWAS),
variant effect predictor, transcription factor ChIP-seq, and
motifbreakR data, we identified candidate gene-CCV
interactions at each locus. This included risk loci where
TWAS identified one or more candidate susceptibility genes
(e.g., HOXD-AS2, HOXD8, and HOXD3 at 2q31) and other loci
where no candidate gene was identified (e.g., MYC and PVT1
at 8q24) by TWAS. In summary, this study describes a
functional framework and provides a greater understanding of
the biological significance of risk alleles and candidate
gene targets at EOC susceptibility loci identified by a
genome-wide association study.},
keywords = {GWAS (Other) / epithelial ovarian cancer risk (Other) /
fine mapping (Other) / functional mechanisms (Other)},
cin = {C020},
ddc = {570},
cid = {I:(DE-He78)C020-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38723632},
doi = {10.1016/j.ajhg.2024.04.011},
url = {https://inrepo02.dkfz.de/record/290096},
}