TY  - JOUR
AU  - Dareng, Eileen O
AU  - Coetzee, Simon G
AU  - Tyrer, Jonathan P
AU  - Peng, Pei-Chen
AU  - Rosenow, Will
AU  - Chen, Stephanie
AU  - Davis, Brian D
AU  - Dezem, Felipe Segato
AU  - Seo, Ji-Heui
AU  - Nameki, Robbin
AU  - Reyes, Alberto L
AU  - Aben, Katja K H
AU  - Anton-Culver, Hoda
AU  - Antonenkova, Natalia N
AU  - Aravantinos, Gerasimos
AU  - Bandera, Elisa V
AU  - Beane Freeman, Laura E
AU  - Beckmann, Matthias W
AU  - Beeghly-Fadiel, Alicia
AU  - Benitez, Javier
AU  - Bernardini, Marcus Q
AU  - Bjorge, Line
AU  - Black, Amanda
AU  - Bogdanova, Natalia V
AU  - Bolton, Kelly L
AU  - Brenton, James D
AU  - Budzilowska, Agnieszka
AU  - Butzow, Ralf
AU  - Cai, Hui
AU  - Campbell, Ian
AU  - Cannioto, Rikki
AU  - Chang-Claude, Jenny
AU  - Chanock, Stephen J
AU  - Chen, Kexin
AU  - Chenevix-Trench, Georgia
AU  - Chiew, Yoke-Eng
AU  - Cook, Linda S
AU  - DeFazio, Anna
AU  - Dennis, Joe
AU  - Doherty, Jennifer A
AU  - Dörk, Thilo
AU  - du Bois, Andreas
AU  - Dürst, Matthias
AU  - Eccles, Diana M
AU  - Ene, Gabrielle
AU  - Fasching, Peter A
AU  - Flanagan, James M
AU  - Fortner, Renée T
AU  - Fostira, Florentia
AU  - Gentry-Maharaj, Aleksandra
AU  - Giles, Graham G
AU  - Goodman, Marc T
AU  - Gronwald, Jacek
AU  - Haiman, Christopher A
AU  - Håkansson, Niclas
AU  - Heitz, Florian
AU  - Hildebrandt, Michelle A T
AU  - Høgdall, Estrid
AU  - Høgdall, Claus K
AU  - Huang, Ruea-Yea
AU  - Jensen, Allan
AU  - Jones, Michael E
AU  - Kang, Daehee
AU  - Karlan, Beth Y
AU  - Karnezis, Anthony N
AU  - Kelemen, Linda E
AU  - Kennedy, Catherine J
AU  - Khusnutdinova, Elza K
AU  - Kiemeney, Lambertus A
AU  - Kjaer, Susanne K
AU  - Kupryjanczyk, Jolanta
AU  - Labrie, Marilyne
AU  - Lambrechts, Diether
AU  - Larson, Melissa C
AU  - Le, Nhu D
AU  - Lester, Jenny
AU  - Li, Lian
AU  - Lubiński, Jan
AU  - Lush, Michael
AU  - Marks, Jeffrey R
AU  - Matsuo, Keitaro
AU  - May, Taymaa
AU  - McLaughlin, John R
AU  - McNeish, Iain A
AU  - Menon, Usha
AU  - Missmer, Stacey
AU  - Modugno, Francesmary
AU  - Moffitt, Melissa
AU  - Monteiro, Alvaro N
AU  - Moysich, Kirsten B
AU  - Narod, Steven A
AU  - Nguyen-Dumont, Tu
AU  - Odunsi, Kunle
AU  - Olsson, Håkan
AU  - Onland-Moret, N Charlotte
AU  - Park, Sue K
AU  - Pejovic, Tanja
AU  - Permuth, Jennifer B
AU  - Piskorz, Anna
AU  - Prokofyeva, Darya
AU  - Riggan, Marjorie J
AU  - Risch, Harvey A
AU  - Rodríguez-Antona, Cristina
AU  - Rossing, Mary Anne
AU  - Sandler, Dale P
AU  - Setiawan, V Wendy
AU  - Shan, Kang
AU  - Song, Honglin
AU  - Southey, Melissa C
AU  - Steed, Helen
AU  - Sutphen, Rebecca
AU  - Swerdlow, Anthony J
AU  - Teo, Soo Hwang
AU  - Terry, Kathryn L
AU  - Thompson, Pamela J
AU  - Vestrheim Thomsen, Liv Cecilie
AU  - Titus, Linda
AU  - Trabert, Britton
AU  - Travis, Ruth
AU  - Tworoger, Shelley S
AU  - Valen, Ellen
AU  - Van Nieuwenhuysen, Els
AU  - Edwards, Digna Velez
AU  - Vierkant, Robert A
AU  - Webb, Penelope M
AU  - Weinberg, Clarice R
AU  - Weise, Rayna Matsuno
AU  - Wentzensen, Nicolas
AU  - White, Emily
AU  - Winham, Stacey J
AU  - Wolk, Alicja
AU  - Woo, Yin-Ling
AU  - Wu, Anna H
AU  - Yan, Li
AU  - Yannoukakos, Drakoulis
AU  - Zeinomar, Nur
AU  - Zheng, Wei
AU  - Ziogas, Argyrios
AU  - Berchuck, Andrew
AU  - Goode, Ellen L
AU  - Huntsman, David G
AU  - Pearce, Celeste L
AU  - Ramus, Susan J
AU  - Sellers, Thomas A
AU  - Freedman, Matthew L
AU  - Lawrenson, Kate
AU  - Schildkraut, Joellen M
AU  - Hazelett, Dennis
AU  - Plummer, Jasmine T
AU  - Kar, Siddhartha
AU  - Jones, Michelle R
AU  - Pharoah, Paul D P
AU  - Gayther, Simon A
TI  - Integrative multi-omics analyses to identify the genetic and functional mechanisms underlying ovarian cancer risk regions.
JO  - The American journal of human genetics
VL  - 111
IS  - 6
SN  - 0002-9297
CY  - New York, NY
PB  - Elsevier
M1  - DKFZ-2024-00995
SP  - 1061-1083
PY  - 2024
N1  - 2024 Jun 6;111(6):1061-1083
AB  - 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.
KW  - GWAS (Other)
KW  - epithelial ovarian cancer risk (Other)
KW  - fine mapping (Other)
KW  - functional mechanisms (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:38723632
DO  - DOI:10.1016/j.ajhg.2024.04.011
UR  - https://inrepo02.dkfz.de/record/290096
ER  -