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Application of a Novel Score Test for Genetic Association Incorporating Gene-Gene Interaction Suggests Functionality for Prostate Cancer Susceptibility Regions

  1. Author:
    Ciampa, J.
    Yeager, M.
    Jacobs, K.
    Thun, M. J.
    Gapstur, S.
    Albanes, D.
    Virtamo, J.
    Weinstein, S. J.
    Giovannucci, E.
    Willett, W. C.
    Cancel-Tassin, G.
    Cussenot, O.
    Valeri, A.
    Hunter, D.
    Hoover, R.
    Thomas, G.
    Chanock, S.
    Holmes, C.
    Chatterjee, N.

  2. Author Address

    [Ciampa, Julia; Albanes, Demetrius; Weinstein, Stephanie J.; Hoover, Robert; Chatterjee, Nilanjan] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. [Ciampa, Julia; Holmes, Chris] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [Yeager, Meredith; Jacobs, Kevin; Hunter, David] NCI, Core Genotype Facil, SAIC Frederick Inc, Frederick, MD 21701 USA. [Thun, Michael J.; Gapstur, Susan] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. [Virtamo, Jarmo] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. [Giovannucci, Edward; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Cancel-Tassin, Geraldine; Cussenot, Olivier; Valeri, Antoine] CeRePP Hop Tenon, Assistance Publ Hop Paris, Paris, France. [Thomas, Gilles] Ctr Leon Berard, INSERM, U590, F-69373 Lyon, France. [Chanock, Stephen] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Frederick, MD 21701 USA.;Chatterjee, N (reprint author), NCI, Div Canc Epidemiol & Genet, EPS 8038,6120 Execut Blvd, Rockville, MD 20852 USA;chattern@mail.nih.gov
    1. Year: 2011
    2. Date: Nov
  2. Journal: Human Heredity
    1. 72
    2. 3
    3. Pages: 182-193
  4. Type of Article: Article
  5. ISSN: 0001-5652
  1. Abstract:

    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. Copyright (C) 2011 S. Karger AG, Basel

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External Sources

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  2. DOI: 10.1159/000331222
  3. View record in Web of Science®
  4. WOS: 000297741800004

Library Notes

  1. Fiscal Year: FY2011-2012
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