| Autor: |
Joseph L. Kelley, Michelle A.T. Hildebrandt, Diana Eccles, Karen Lu, Elisa V. Bandera, Steven A. Narod, Linda S. Cook, Matthias W. Beckmann, John R. McLaughlin, Liisa M. Pelttari, Elizabeth M. Poole, Arto Leminen, Jennifer A. Doherty, Argyrios Ziogas, Weiva Sieh, Maria Bisogna, Stuart MacGregor, Andrew Berchuck, Agnieszka Timorek, Ralf Bützow, Hoda Anton-Culver, Robert P. Edwards, Peter Hillemanns, Anja Rudolph, Joseph H. Rothstein, Agnieszka Dansonka-Mieszkowska, Aleksandra Gentry-Maharaj, Ignace Vergote, Louise A. Brinton, Meir J. Stampfer, Honglin Song, Jenny Chang-Claude, Anna Jakubowska, Paul D.P. Pharoah, Lambertus A. Kiemeney, Graham G. Giles, Valerie McGuire, Reidun K. Kopperud, Daniel W. Cramer, Alice S. Whittemore, Jacek Gronwald, Gabriel Cuellar-Partida, Georgia Chenevix-Trench, Ellen L. Goode, Stacey J. Winham, Julie M. Cunningham, Estrid Høgdall, Adriaan Vanderstichele, Jan Lubinski, Lukasz Szafron, Peter A. Fasching, Jonathan Tyrer, Alexander Hein, Harvey A. Risch, Ian G. Campbell, Joellen M. Schildkraut, Shelley S. Tworoger, C. Blake Gilks, Allan Jensen, Natalia Bogdanova, Helga B. Salvesen, Rikki Cannioto, Shan Wang-Gohrke, Terry K. Morgan, Susan J. Ramus, Catherine M. Phelan, Kirsten B. Moysich, Usha Menon, Penelope M. Webb, Angela Brooks-Wilson, Ingo B. Runnebaum, Anna H. Wu, Celeste Leigh Pearce, Suzanne C. Dixon, Dong Liang, Yi Lu, Natalia Antonenkova, Diether Lambrechts, Stacey A. Missmer, Brooke L. Fridley, Roberta B. Ness, Mary Anne Rossing, Thilo Dörk, Stefanie Burghaus, Douglas A. Levine, Marc T. Goodman, Susanne K. Kjaer, Britton Trabert, Kathryn L. Terry, Claus Høgdall, Tomasz Kluz, Heli Nevanlinna, Line Bjørge, Francesmary Modugno, Jolanta Lissowska, Fanny Dao, Simon A. Gayther, Katja K.H. Aben, Leon F.A.G. Massuger, Fiona Bruinsma, Xifeng Wu, Matthias Dürst, Jolanta Kupryjanczyk, Nicolas Wentzensen, Katharina Bischof, Els Van Nieuwenhuysen, Nhu D. Le, Sara H. Olson |
| Rok vydání: |
2016 |
| Předmět: |
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| Zdroj: |
Human genetics, vol 135, iss 7
Human Genetics, 135, 741-56
Human Genetics, 135, 7, pp. 741-56 |
| ISSN: |
0340-6717 |
| Popis: |
Contains fulltext : 171782.pdf (Publisher’s version ) (Closed access) Epithelial ovarian cancer (EOC) is one of the deadliest common cancers. The five most common types of disease are high-grade and low-grade serous, endometrioid, mucinous and clear cell carcinoma. Each of these subtypes present distinct molecular pathogeneses and sensitivities to treatments. Recent studies show that certain genetic variants confer susceptibility to all subtypes while other variants are subtype-specific. Here, we perform an extensive analysis of the genetic architecture of EOC subtypes. To this end, we used data of 10,014 invasive EOC patients and 21,233 controls from the Ovarian Cancer Association Consortium genotyped in the iCOGS array (211,155 SNPs). We estimate the array heritability (attributable to variants tagged on arrays) of each subtype and their genetic correlations. We also look for genetic overlaps with factors such as obesity, smoking behaviors, diabetes, age at menarche and height. We estimated the array heritabilities of high-grade serous disease ([Formula: see text] = 8.8 +/- 1.1 %), endometrioid ([Formula: see text] = 3.2 +/- 1.6 %), clear cell ([Formula: see text] = 6.7 +/- 3.3 %) and all EOC ([Formula: see text] = 5.6 +/- 0.6 %). Known associated loci contributed approximately 40 % of the total array heritability for each subtype. The contribution of each chromosome to the total heritability was not proportional to chromosome size. Through bivariate and cross-trait LD score regression, we found evidence of shared genetic backgrounds between the three high-grade subtypes: serous, endometrioid and undifferentiated. Finally, we found significant genetic correlations of all EOC with diabetes and obesity using a polygenic prediction approach. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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Full text from SpringerLink 