Hum Hered 2007;63:175–186

Adaptive Two-Stage Analysis of Genetic Association in Case-Control Designs

Zheng G.a · Song K.b · Elston R.C.c
aOffice of Biostatistics Research, National Heart, Lung and Blood Institute, Bethesda, Md., bGlaxoSmithKline, King of Prussia, Pa., and cDepartment of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA
email Corresponding Author

 goto top of outline Key Words

  • Conditional power
  • Genomewide association
  • Hardy-Weinberg disequilibrium
  • Self-replication
  • Trend test

 goto top of outline Abstract

We study a two-stage analysis of genetic association for case-control studies. In the first stage, we compare Hardy-Weinberg disequilibrium coefficients between cases and controls and, in the second stage, we apply the Cochran- Armitage trend test. The two analyses are statistically independent when Hardy-Weinberg equilibrium holds in the population, so all the samples are used in both stages. The significance level in the first stage is adaptively determined based on its conditional power. Given the level in the first stage, the level for the second stage analysis is determined with the overall Type I error being asymptotically controlled. For finite sample sizes, a parametric bootstrap method is used to control the overall Type I error rate. This two-stage analysis is often more powerful than the Cochran-Armitage trend test alone for a large association study. The new approach is applied to SNPs from a real study.

Copyright © 2007 S. Karger AG, Basel

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 goto top of outline Author Contacts

Dr. Gang Zheng
Office of Biostatistics Research, Division of Epidemiology and Clinical Applications
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Bethesda, MD 20892 (USA)
Tel. +1 301 435 1287, Fax +1 301 480 1862, E-Mail

 goto top of outline Article Information

Received: September 11, 2006
Accepted after revision: November 29, 2006
Published online: February 19, 2007
Number of Print Pages : 12
Number of Figures : 4, Number of Tables : 6, Number of References : 31

 goto top of outline Publication Details

Human Heredity (International Journal of Human and Medical Genetics)

Vol. 63, No. 3-4, Year 2007 (Cover Date: March 2007)

Journal Editor: Devoto, M. (Philadelphia, Pa.)
ISSN: 0001–5652 (print), 1423–0062 (Online)

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