Hum Hered 2003;55:56–65

Estimation and Tests of Haplotype-Environment Interaction when Linkage Phase Is Ambiguous

Lake S.L.a,b · Lyon H.a · Tantisira K.a · Silverman E.K.a · Weiss S.T.a,c · Laird N.M.d · Schaid D.J.e
aChanning Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.; bEigenStat, Brookline, Mass.; cHarvard-Partners Center for Genetics and Genomics, Partners Health Care, Boston, Mass.; dDepartment of Biostatistics, Harvard School of Public Health, Boston, Mass., and eDepartments of Health Sciences Research and Medical Genetics, Mayo Clinic/Foundation, Rochester, Minn., USA
email Corresponding Author

 goto top of outline Key Words

  • Haplotype
  • Association
  • Gene-environment interaction
  • Generalized linear model

 goto top of outline Abstract

In the study of complex traits, the utility of linkage analysis and single marker association tests can be limited for researchers attempting to elucidate the complex interplay between a gene and environmental covariates. For these purposes, tests of gene-environment interactions are needed. In addition, recent studies have indicated that haplotypes, which are specific combinations of nucleotides on the same chromosome, may be more suitable as the unit of analysis for statistical tests than single genetic markers. The difficulty with this approach is that, in standard laboratory genotyping, haplotypes are often not directly observable. Instead, unphased marker phenotypes are collected. In this article, we present a method for estimating and testing haplotype-environment interactions when linkage phase is potentially ambiguous. The method builds on the work of Schaid et al. [2002] and is applicable to any trait that can be placed in the generalized linear model framework. Simulations were run to illustrate the salient features of the method. In addition, the method was used to test for haplotype-smoking exposure interaction with data from the Childhood Asthma Management Program.

Copyright © 2003 S. Karger AG, Basel

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 goto top of outline Author Contacts

Dr. Stephen Lake
Channing Laboratory
181 Longwood Avenue
Boston, MA 02115 (USA)
Tel. +1 617 596 6936, Fax +1 617 525 0958, E-Mail

 goto top of outline Article Information

Received: March 6, 2003
Accepted: May 7, 2003
Number of Print Pages : 10
Number of Figures : 0, Number of Tables : 4, Number of References : 41

 goto top of outline Publication Details

Human Heredity (International Journal of Human and Medical Genetics)
Founded 1950 as Acta Genetica et Statistica Medica by Gunnar Dahlberg; Continued by M. Hauge (1965–1983)

Vol. 55, No. 1, Year 2003 (Cover Date: Released August 2003)

Journal Editor: J. Ott, New York, N.Y.
ISSN: 0001–5652 (print), 1423–0062 (Online)

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