A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk
| العنوان: | A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk |
|---|---|
| المؤلفون: | Adriaan Vanderstichele, Kenneth Offit, Anna H. Wu, Claudine Isaacs, Mary B. Daly, Jamie K. Teer, Jacek Gronwald, Diana Eccles, Heli Nevanlinna, Javier Benitez, Dale P. Sandler, Maria A. Caligo, Priyanka Sharma, Mary Anne Rossing, Thilo Dörk, Hae Kyung Im, Hoda Anton-Culver, Fergus J. Couch, Douglas A. Levine, Judy Garber, Marc Tischkowitz, Edith Olah, Ute Hamann, Rita K. Schmutzler, Soo Hwang Teo, Ralf Bützow, Amanda E. Toland, Robert L. Nussbaum, Michael T. Parsons, Drakoulis Yannoukakos, Jeffrey N. Weitzel, Georgia Chenevix-Trench, Francesmary Modugno, Yingchang Lu, Manuel R. Teixeira, Jirong Long, Honglin Song, Antonis C. Antoniou, Susan J. Ramus, Elizabeth J. van Rensburg, Gad Rennert, Douglas F. Easton, Evgeny N. Imyanitov, Andrew Berchuck, Tanja Pejovic, Amanda B. Spurdle, Florian Heitz, Catherine M. Phelan, Nhu D. Le, Lang Wu, David G. Huntsman, Renée T. Fortner, Beth Y. Karlan, Irene L. Andrulis, Matti A. Rookus, Anthony J. Swerdlow, Miguel Angel Pujana, Christian F. Singer, Amalia Mattiello, George Fountzilas, Banu Arun, Shelley S. Tworoger, Graham G. Giles, Liene Nikitina-Zake, Kirsten B. Moysich, Nadine Tung, Mads Thomassen, Trinidad Caldés, Wei Zheng, Digna R. Velez Edwards, Kathleen Claes, Nicolas Wentzensen, Gustavo C. Rodriguez, Thomas A. Sellers, Ellen L. Goode, Daniel R. Barnes, Susan L. Neuhausen, Alicja Wolk, Andrew K. Godwin, Taymaa May, Olufunmilayo I. Olopade, Yian Ann Chen, Brett M. Reid, Line Bjørge, Fabienne Lesueur, Weiva Sieh, Kristin K. Zorn, Jacques Simard, Peter J. Hulick, Melissa C. Southey, Finn Cilius Nielsen, Ava Kwong, Sue K. Park, Joellen M. Schildkraut, Peter A. Fasching, Lesley McGuffog, Ana Vega, Antonia Trichopoulou, David E. Goldgar, Anna Jakubowska, Paul D.P. Pharoah, Paul A. James, Claus Høgdall, Lambertus A. Kiemeney, Susanne K. Kjaer, Sara H. Olson, Ana Osorio, Jenny Chang-Claude, Cristina Rodríguez-Antona, Isabelle Romieu, Iwona K. Rzepecka, Iain A. McNeish, Xingyi Guo, Eitan Friedman, Marco Montagna, Marc T. Goodman, Goska Leslie, Melissa A. Merritt, Emily White, Penelope M. Webb, Jennifer B. Permuth, Patricia A. Ganz, Antoinette Hollestelle, Paolo Peterlongo, Alicia Beeghly-Fadiel, Rebecca Sutphen, Michelle A.T. Hildebrandt, Joe Dennis, Petra H.M. Peeters, Veronica Wendy Setiawan, Susan M. Domchek, Rosa B. Barkardottir, Simon A. Gayther, Mark H. Greene, Harvey A. Risch, Orland Diez, Anna deFazio, Ian G. Campbell, Daniel W. Cramer, Linda E. Kelemen, Elisa V. Bandera, Bingshan Li, Håkan Olsson, James D. Brenton |
| المساهمون: | Medical Oncology |
| المصدر: | Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid Consejería de Sanidad de la Comunidad de Madrid Cancer Research, 78(18), 5419-5430. American Association for Cancer Research Inc. Cancer Research, 78(18), 5419. American Association for Cancer Research Inc. Lu, Y, Beeghly-Fadiel, A, Wu, L, Guo, X, Li, B, Schildkraut, J M, Im, H K, Chen, Y A, Permuth, J B, Reid, B M, Teer, J K, Moysich, K B, Andrulis, I L, Anton-Culver, H, Arun, B K, Bandera, E V, Barkardottir, R B, Barnes, D R, Benitez, J, Bjorge, L, Brenton, J, Butzow, R, Caldes, T, Caligo, M A, Campbell, I, Chang-Claude, J, Claes, K B M, Couch, F J, Cramer, D W, Daly, M B, deFazio, A, Dennis, J, Diez, O, Domchek, S M, Dörk, T, Easton, D F, Eccles, D M, Fasching, P A, Fortner, R T, Fountzilas, G, Friedman, E, Ganz, P A, Garber, J, Giles, G G, Godwin, A K, Goldgar, D E, Goodman, M T, Greene, M H, Gronwald, J, Hamann, U, Heitz, F, Hildebrandt, M A T, Høgdall, C K, Hollestelle, A, Hulick, P J, Huntsman, D G, Imyanitov, E N, Isaacs, C, Jakubowska, A, James, P, Karlan, B Y, Kelemen, L E, Kiemeney, L A, Kjaer, S K, Kwong, A, Le, N D, Leslie, G, Lesueur, F, Levine, D A, Mattiello, A, May, T, McGuffog, L, McNeish, I A, Merritt, M A, Modugno, F, Montagna, M, Neuhausen, S L, Nevanlinna, H, Nielsen, F C, Nikitina-Zake, L, Nussbaum, R L, Offit, K, Olah, E, Olopade, O I, Olson, S H, Olsson, H, Osorio, A, Park, S K, Parsons, M T, Peeters, P H M, Pejovic, T, Peterlongo, P, Phelan, C M, Pujana, M A, Ramus, S J, Rennert, G, Risch, H, Rodriguez, G C, Rodríguez-Antona, C, Romieu, I, Rookus, M A, Rossing, M A, Rzepecka, I K, Sandler, D P, Schmutzler, R K, Setiawan, V W, Sharma, P, Sieh, W, Simard, J, Singer, C F, Song, H, Southey, M C, Spurdle, A B, Sutphen, R, Swerdlow, A J, Teixeira, M R, Teo, S H, Thomassen, M, Tischkowitz, M, Toland, A E, Trichopoulou, A, Tung, N, Tworoger, S S, van Rensburg, E J, Vanderstichele, A, Vega, A, Edwards, D V, Webb, P M, Weitzel, J N, Wentzensen, N, White, E, Wolk, A, Wu, A H, Yannoukakos, D, Zorn, K K, Gayther, S A, Antoniou, A C, Berchuck, A, Goode, E L, Chenevix-Trench, G, Sellers, T A, Pharoah, P D P, Zheng, W & Long, J 2018, ' A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk ', Cancer Research, vol. 78, no. 18, pp. 5419-5430 . https://doi.org/10.1158/0008-5472.CAN-18-0951Test Cancer Research, 78, 5419-5430 Cancer Research, 78, 18, pp. 5419-5430 |
| بيانات النشر: | American Association for Cancer Research Inc., 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, endocrine system diseases, Carcinogenesis, LOCI, Genome-wide association study, CORTICOTROPIN-RELEASING HORMONE, Carcinoma, Ovarian Epithelial, VARIANTS, Transcriptome, Cohort Studies, Risk Factors, MULTIPLE, GWAS, Genetics, Ovarian Neoplasms, Prognosis, female genital diseases and pregnancy complications, 3. Good health, HOXB2, Oncology, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Female, Life Sciences & Biomedicine, EXPRESSION, Genotype, Quantitative Trait Loci, Locus (genetics), Quantitative trait locus, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Journal Article, Humans, BREAST-CANCER, Genetic Predisposition to Disease, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Gene, Genotyping, Genetic association, Science & Technology, IDENTIFICATION, Gene Expression Profiling, Gene expression profiling, 030104 developmental biology, IN-VITRO FERTILIZATION, Genome-Wide Association Study |
| الوصف: | 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. |
| وصف الملف: | image/pdf; application/pdf |
| تدمد: | 1538-7445 0008-5472 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ecdbedfd46ce7dc61703d021c46fbd49Test https://pure.eur.nl/en/publications/0cc4c420-88d2-48c1-b49c-4f934152bddcTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ecdbedfd46ce7dc61703d021c46fbd49 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
|---|