Polygenic Risk Modelling for Prediction of Epithelial Ovarian Cancer Risk
Creators: name: Dareng, Eileen O
name: Tyrer, Jonathan
name: Barnes, Daniel
name: Jones, Michelle R
name: Yang, Xin
name: Aben, Katja KH
name: Adank, Muriel A
name: Agata, Simona
name: Andrulis, Irene L
name: Anton-Culver, Hoda
name: Antonenkova, Natalia N
name: Aravantinos, Gerasimos
name: Arun, Banu K
name: Augustinsson, Annelie
name: Balmaña, Judith
name: Bandera, Elisa V
name: Barkardottir, Rosa B
name: Barrowdale, Daniel
name: Beckmann, Matthias W
name: Beeghly-Fadiel, Alicia
name: Benitez, Javier
name: Bermisheva, Marina
name: Bernardini, Marcus Q
name: Bjorge, Line
name: Black, Amanda
name: Bogdanova, Natalia V
name: Bonanni, Bernardo
name: Borg, Ake
name: Brenton, James
name: Budzilowska, Agnieszka
name: Butzow, Ralf
name: Buys, Saundra S
name: Cai, Hui
name: Caligo, Maria A
name: Campbell, Ian
name: Cannioto, Rikki
name: Cassingham, Hayley
name: Chang-Claude, Jenny
name: Chanock, Stephen J
name: Chen, Kexin
name: Chiew, Yoke-Eng
name: Chung, Wendy K
name: Claes, Kathleen BM
name: Colanna, Sarah
name: Cook, Linda S
name: Couch, Fergus J
name: Daly, Mary B
name: Dao, Fanny
name: Davies, Eleanor
name: De La Hoya, Miguel
name: Putter, Robin De
name: Dennis, Joe
name: DePersia, Allison
name: Devilee, Peter
name: Diez, Orland
name: Ding, Yuan Chun
name: Doherty, Jennifer A
name: Domchek, Susan M
name: Dörk, Thilo
name: Bois, Andreas Du
name: Dürst, Matthias
name: Eccles, Diana M
name: Eliassen, Heather A
name: Engel, Christoph
name: Evans, D Gareth
name: Fasching, Peter A
name: Flanagan, James M
name: Foretova, Lenka
name: Fortner, Renée T
name: Friedman, Eitan
name: Ganz, Patricia A
name: Garber, Judy
name: Gensini, Francesca
name: Giles, Graham G
name: Glendon, Gord
name: Godwin, Andrew K
name: Goodman, Marc T
name: Greene, Mark H
name: Gronwald, Jacek
name: Hahnen, Eric
name: Haiman, Christopher A
name: Håkansson, Niclas
name: Hamann, Ute
name: Hansen, Thomas VO
name: Harris, Holly R
name: Hartman, Mikael
name: Heitz, Florian
name: Hildebrandt, Michelle AT
name: Høgdall, Estrid
name: Høgdall, Claus K
name: Hopper, John L
name: Huang, Ruea-Yea
name: Huff, Chad
name: Hulick, Peter J
name: Huntsman, David G
name: Imyanitov, Evgeny N
name: Isaacs, Claudine
name: Jakubowska, Anna
name: James, Paul A
name: Janavicius, Ramunas
name: Jensen, Allan
name: Johannsson, Oskar Th
name: John, Esther M
name: Jones, Michael E
name: Kang, Daehee
name: Karlan, Beth Y
name: Karnezis, Anthony
name: Kelemen, Linda E
name: Khusnutdinova, Elza
name: Kiemeney, Lambertus A
name: Kim, Byoung-Gie
name: Kjaer, Susanne K
name: Komenaka, Ian
name: Kupryjanczyk, Jolanta
name: Kurian, Allison W
name: Kwong, Ava
name: Lambrechts, Diether
name: Larson, Melissa C
name: Lazaro, Conxi
name: Le, Nhu D
name: Leslie, Goska
name: Lester, Jenny
name: Lesueur, Fabienne
name: Levine, Douglas A
name: Li, Lian
name: Li, Jingmei
name: Loud, Jennifer T
name: Lu, Karen H
name: Lubiński, Jan
name: Machackova, Eva
name: Mai, Phuong L
name: Manoukian, Siranoush
name: Marks, Jeffrey R
name: Matsuno, Rayna Kim
name: Matsuo, Keitaro
name: May, Taymaa
name: McGuffog, Lesley
name: McLaughlin, John R
name: McNeish, Iain A
name: Mebirouk, Noura
name: Menon, Usha
name: Miller, Austin
name: Milne, Roger L
name: Minlikeeva, Albina
name: Modugno, Francesmary
name: Montagna, Marco
name: Moysich, Kirsten B
name: Munro, Elizabeth
name: Nathanson, Katherine L
name: Neuhausen, Susan L
name: Nevanlinna, Heli
name: Yie, Joanne Ngeow Yuen
name: Nielsen, Henriette Roed
name: Nielsen, Finn C
name: Nikitina-Zake, Liene
name: Odunsi, Kunle
name: Offit, Kenneth
name: Olah, Edith
name: Olbrecht, Siel
name: Olopade, Olufunmilayo I
name: Olson, Sara H
name: Olsson, Håkan
name: Osorio, Ana
name: Papi, Laura
name: Park, Sue K
name: Parsons, Michael T
name: Pathak, Harsha
name: Pedersen, Inge Sokilde
name: Peixoto, Ana
name: Pejovic, Tanja
name: Perez-Segura, Pedro
name: Permuth, Jennifer B
name: Peshkin, Beth
name: Peterlongo, Paolo
name: Piskorz, Anna
name: Prokofyeva, Darya
name: Radice, Paolo
name: Rantala, Johanna
name: Riggan, Marjorie J
name: Risch, Harvey A
name: Rodriguez-Antona, Cristina
name: Ross, Eric
name: Rossing, Mary Anne
name: Runnebaum, Ingo
name: Sandler, Dale P
name: Santamariña, Marta
name: Soucy, Penny
name: Schmutzler, Rita K
name: Setiawan, V Wendy
name: Shan, Kang
name: Sieh, Weiva
name: Simard, Jacques
name: Singer, Christian F
name: Sokolenko, Anna P
name: Song, Honglin
name: Southey, Melissa C
name: Steed, Helen
name: Stoppa-Lyonnet, Dominique
name: Sutphen, Rebecca
name: Swerdlow, Anthony J
name: Tan, Yen Yen
name: Teixeira, Manuel R
name: Teo, Soo Hwang
name: Terry, Kathryn L
name: Terry, Mary Beth
name: Thomassen, Mads
name: Thompson, Pamela J
name: Vestrheim Thomsen, Liv Cecilie
name: Thull, Darcy L
name: Tischkowitz, Marc
name: Titus, Linda
name: Toland, Amanda E
name: Torres, Diana
name: Trabert, Britton
name: Travis, Ruth
name: Tung, Nadine
name: Tworoger, Shelley S
name: Valen, Ellen
name: Van Altena, Anne M
name: Van Der Hout, Annemieke H
name: Van Nieuwenhuysen, Els
name: Van Rensburg, Elizabeth J
name: Vega, Ana
name: Edwards, Digna Velez
name: Vierkant, Robert A
name: Wang, Frances
name: Wappenschmidt, Barbara
name: Webb, Penelope M
name: Weinberg, Clarice R
name: Weitzel, Jeffrey N
name: Wentzensen, Nicolas
name: White, Emily
name: Whittemore, Alice S
name: Winham, Stacey J
name: Wolk, Alicja
name: Woo, Yin-Ling
name: Wu, Anna H
name: Yan, Li
name: Yannoukakos, Drakoulis
name: Zavaglia, Katia M
name: Zheng, Wei
name: Ziogas, Argyrios
name: Zorn, Kristin K
name: Easton, Douglas
name: Lawrenson, Kate
name: DeFazio, Anna
name: Sellers, Thomas A
name: Ramus, Susan J
name: Pearce, Celeste L
name: Monteiro, Alvaro N
name: Cunningham, Julie
name: Goode, Ellen L
name: Schildkraut, Joellen M
name: Berchuck, Andrew
name: Chenevix-Trench, Georgia
name: Gayther, Simon A
name: Antoniou, Antonis C
name: Pharoah, Paul DP
Publisher: name: Apollo - University of Cambridge Repository
Year: 2022
Subjects: Article
/692/499
/631/208/2489
/631/208/721
/45/43
/45/61
article

description: Funder: Funding details are provided in the Supplementary Material
description: AbstractPolygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally-efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, “select and shrink for summary statistics” (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestry; 7,669 women of East Asian ancestry; 1,072 women of African ancestry, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestry. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38(95%CI:1.28–1.48,AUC:0.588) per unit standard deviation, in women of European ancestry; 1.14(95%CI:1.08–1.19,AUC:0.538) in women of East Asian ancestry; 1.38(95%CI:1.21-1.58,AUC:0.593) in women of African ancestry; hazard ratios of 1.37(95%CI:1.30–1.44,AUC:0.592) in BRCA1 pathogenic variant carriers and 1.51(95%CI:1.36-1.67,AUC:0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.