AIMS: We introduce an innovative multilocus test for disease association. It is an extension of an existing score test that gains power over alternative methods by incorporating a parsimonious one-degree-of-freedom model for interaction. We use our method in applications designed to detect interactions that generate hypotheses about the functionality of prostate cancer (PRCA) susceptibility regions. METHODS: Our proposed score test is designed to gain additional power through the use of a retrospective likelihood that exploits an assumption of independence between unlinked loci in the underlying population. Its performance is validated through simulation. The method is used in conditional scans with data from stage II of the Cancer Genetic Markers of Susceptibility PRCA genome-wide association study. RESULTS: Our proposed method increases power to detect susceptibility loci in diverse settings. It identified two high-ranking, biologically interesting interactions: (1) rs748120 of NR2C2 and subregions of 8q24 that contain independent susceptibility loci specific to PRCA and (2) rs4810671 of SULF2 and both JAZF1 and HNF1B that are associated with PRCA and type 2 diabetes. CONCLUSIONS: Our score test is a promising multilocus tool for genetic epidemiology. The results of our applications suggest functionality for poorly understood PRCA susceptibility regions. They motivate replication study.
AIMS: We introduce an innovative multilocus test for disease association. It is an extension of an existing score test that gains power over alternative methods by incorporating a parsimonious one-degree-of-freedom model for interaction. We use our method in applications designed to detect interactions that generate hypotheses about the functionality of prostate cancer (PRCA) susceptibility regions. METHODS: Our proposed score test is designed to gain additional power through the use of a retrospective likelihood that exploits an assumption of independence between unlinked loci in the underlying population. Its performance is validated through simulation. The method is used in conditional scans with data from stage II of the Cancer Genetic Markers of Susceptibility PRCA genome-wide association study. RESULTS: Our proposed method increases power to detect susceptibility loci in diverse settings. It identified two high-ranking, biologically interesting interactions: (1) rs748120 of NR2C2 and subregions of 8q24 that contain independent susceptibility loci specific to PRCA and (2) rs4810671 of SULF2 and both JAZF1 and HNF1B that are associated with PRCA and type 2 diabetes. CONCLUSIONS: Our score test is a promising multilocus tool for genetic epidemiology. The results of our applications suggest functionality for poorly understood PRCA susceptibility regions. They motivate replication study.
Authors: Julius Gudmundsson; Patrick Sulem; Valgerdur Steinthorsdottir; Jon T Bergthorsson; Gudmar Thorleifsson; Andrei Manolescu; Thorunn Rafnar; Daniel Gudbjartsson; Bjarni A Agnarsson; Adam Baker; Asgeir Sigurdsson; Kristrun R Benediktsdottir; Margret Jakobsdottir; Thorarinn Blondal; Simon N Stacey; Agnar Helgason; Steinunn Gunnarsdottir; Adalheidur Olafsdottir; Kari T Kristinsson; Birgitta Birgisdottir; Shyamali Ghosh; Steinunn Thorlacius; Dana Magnusdottir; Gerdur Stefansdottir; Kristleifur Kristjansson; Yu Bagger; Robert L Wilensky; Muredach P Reilly; Andrew D Morris; Charlotte H Kimber; Adebowale Adeyemo; Yuanxiu Chen; Jie Zhou; Wing-Yee So; Peter C Y Tong; Maggie C Y Ng; Torben Hansen; Gitte Andersen; Knut Borch-Johnsen; Torben Jorgensen; Alejandro Tres; Fernando Fuertes; Manuel Ruiz-Echarri; Laura Asin; Berta Saez; Erica van Boven; Siem Klaver; Dorine W Swinkels; Katja K Aben; Theresa Graif; John Cashy; Brian K Suarez; Onco van Vierssen Trip; Michael L Frigge; Carole Ober; Marten H Hofker; Cisca Wijmenga; Claus Christiansen; Daniel J Rader; Colin N A Palmer; Charles Rotimi; Juliana C N Chan; Oluf Pedersen; Gunnar Sigurdsson; Rafn Benediktsson; Eirikur Jonsson; Gudmundur V Einarsson; Jose I Mayordomo; William J Catalona; Lambertus A Kiemeney; Rosa B Barkardottir; Jeffrey R Gulcher; Unnur Thorsteinsdottir; Augustine Kong; Kari Stefansson Journal: Nat Genet Date: 2007-07-01 Impact factor: 38.330
Authors: Samsiddhi Bhattacharjee; Zhaoming Wang; Julia Ciampa; Peter Kraft; Stephen Chanock; Kai Yu; Nilanjan Chatterjee Journal: Am J Hum Genet Date: 2010-03-04 Impact factor: 11.025
Authors: Amy Strange; Francesca Capon; Chris C A Spencer; Jo Knight; Michael E Weale; Michael H Allen; Anne Barton; Gavin Band; Céline Bellenguez; Judith G M Bergboer; Jenefer M Blackwell; Elvira Bramon; Suzannah J Bumpstead; Juan P Casas; Michael J Cork; Aiden Corvin; Panos Deloukas; Alexander Dilthey; Audrey Duncanson; Sarah Edkins; Xavier Estivill; Oliver Fitzgerald; Colin Freeman; Emiliano Giardina; Emma Gray; Angelika Hofer; Ulrike Hüffmeier; Sarah E Hunt; Alan D Irvine; Janusz Jankowski; Brian Kirby; Cordelia Langford; Jesús Lascorz; Joyce Leman; Stephen Leslie; Lotus Mallbris; Hugh S Markus; Christopher G Mathew; W H Irwin McLean; Ross McManus; Rotraut Mössner; Loukas Moutsianas; Asa T Naluai; Frank O Nestle; Giuseppe Novelli; Alexandros Onoufriadis; Colin N A Palmer; Carlo Perricone; Matti Pirinen; Robert Plomin; Simon C Potter; Ramon M Pujol; Anna Rautanen; Eva Riveira-Munoz; Anthony W Ryan; Wolfgang Salmhofer; Lena Samuelsson; Stephen J Sawcer; Joost Schalkwijk; Catherine H Smith; Mona Ståhle; Zhan Su; Rachid Tazi-Ahnini; Heiko Traupe; Ananth C Viswanathan; Richard B Warren; Wolfgang Weger; Katarina Wolk; Nicholas Wood; Jane Worthington; Helen S Young; Patrick L J M Zeeuwen; Adrian Hayday; A David Burden; Christopher E M Griffiths; Juha Kere; André Reis; Gilean McVean; David M Evans; Matthew A Brown; Jonathan N Barker; Leena Peltonen; Peter Donnelly; Richard C Trembath Journal: Nat Genet Date: 2010-10-17 Impact factor: 38.330
Authors: Ming Liu; Xiaohong Shi; Fan Yang; Jianye Wang; Yong Xu; Dong Wei; Kuo Yang; Yaoguang Zhang; Xin Wang; Siying Liang; Xin Chen; Liang Sun; Xiaoquan Zhu; Chengxiao Zhao; Ling Zhu; Lei Tang; Chenguang Zheng; Ze Yang Journal: Int J Environ Res Public Health Date: 2016-01-27 Impact factor: 3.390