Robust trend tests for genetic association using matched case-control design

Gang Zheng, Xin Tian, Steven E. Weinberger, Patricia Finn, Erik Garpestad, Allison Moran, Henry Yeager, David L. Rabin, Susan Stein, Michael C. Iannuzzi, Benjamin A. Rybicki, Marcie Major, Mary Maliarik, John Popovich, David R. Moller, Carol J. Johns, Cynthia Rand, Joanne Steimel, Marc A. Judson, Susan D. AlessandroNancy Heister, Theresa Johnson, Daniel T. Lackland, Janardan Pandey, Steven Sahn, Charlie Strange, Alvin S. Teirstein, Louis DePalo, Sheldon Brown, Marvin Lesser, Maria L. Padilla, Marilyn Marshall, Lee S. Newman, Cecile Rose, Juli Barnard, Robert P. Baughman, Elysc E. Lower, Donna B. Winget, Geoffrey McLennan, Gary Hunninghake, Chuck Dayton, Linda Powers, Milton D. Rossman, Eddy A. Bresnitz, Ronald Daniele, Jackie Regovich, William Sexauer, Robert Musson, Joanne Deshler, Paul Sorlie, Margaret Wu, Reuben Cherniak, Lee Newman, Genell L. Knatterud, Michael L. Terrin, Bruce W. Thompson, Kathleen Brown, Margaret Frederick, Frances LoPresti, Patricia Wilkins, Martha Canner, Judy Dotson, Steve Lindenfelser, Mark Cosentino, Mary Maliarik, Robert Baughman, Milton Rossman, Dimitri Monos, Chung Wha Lee, David Moller, Janardan Pandey, Peter Almenoff, Ian Brett, Sheldon Brown, Marvin Lesser, Lee Newman, Brian Kotzin, Geoffrey McLennan, Gary Hunninghake, Patricia Finn, Richard D. Jaffe, Reuben Cherniack, Robert P. Baughman, Joanne Deshler, Marc A. Judson, Genell L. Knatterud, Geoffrey McLennan, David R. Moller, Robert A. Musson, Lee S. Newman, Milton D. Rossman, Alvin S. Teirstein, Michael L. Terrin, William Martin, Takamaru Ashikaga, David B. Coultas, Gerald S. Davis, Fred Gifford

Research output: Contribution to journalArticlepeer-review

Abstract

Trend tests for genetic association using a matched case-control design are studied, which allows for a variable number of controls per case. However, the tests depend on the scores based on the underlying genetic model, thus it may result in substantial loss of power when the model is misspecified. Since the mode of inheritance may be unknown for complex diseases, robust trend tests in matched case-control studies are developed. Simulation is conducted to compare the trend tests and the robust trend tests under various genetic models. The results are applied to detect candidate-gene association using an example from a case-control aetiologic study of sarcoidosis.

Original languageEnglish (US)
Pages (from-to)3160-3173
Number of pages14
JournalStatistics in Medicine
Volume25
Issue number18
DOIs
StatePublished - Sep 30 2006

Keywords

  • Case-control study
  • MAX
  • MERT
  • Score test
  • Variable matching

ASJC Scopus subject areas

  • Epidemiology
  • Statistics and Probability

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