Estimation and tests of haplotype-environment interaction when linkage phase is ambiguous

Stephen L. Lake, H. Lyon, K. Tantisira, E. K. Silverman, S. T. Weiss, N. M. Laird, Daniel J Schaid

Research output: Contribution to journalArticle

368 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)56-65
Number of pages10
JournalHuman Heredity
Volume55
Issue number1
DOIs
StatePublished - 2003

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Haplotypes
Gene-Environment Interaction
Genetic Markers
Linear Models
Asthma
Nucleotides
Chromosomes
Smoking
Research Personnel
Phenotype
Genes

Keywords

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

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Lake, S. L., Lyon, H., Tantisira, K., Silverman, E. K., Weiss, S. T., Laird, N. M., & Schaid, D. J. (2003). Estimation and tests of haplotype-environment interaction when linkage phase is ambiguous. Human Heredity, 55(1), 56-65. https://doi.org/10.1159/000071811

Estimation and tests of haplotype-environment interaction when linkage phase is ambiguous. / Lake, Stephen L.; Lyon, H.; Tantisira, K.; Silverman, E. K.; Weiss, S. T.; Laird, N. M.; Schaid, Daniel J.

In: Human Heredity, Vol. 55, No. 1, 2003, p. 56-65.

Research output: Contribution to journalArticle

Lake, SL, Lyon, H, Tantisira, K, Silverman, EK, Weiss, ST, Laird, NM & Schaid, DJ 2003, 'Estimation and tests of haplotype-environment interaction when linkage phase is ambiguous', Human Heredity, vol. 55, no. 1, pp. 56-65. https://doi.org/10.1159/000071811
Lake SL, Lyon H, Tantisira K, Silverman EK, Weiss ST, Laird NM et al. Estimation and tests of haplotype-environment interaction when linkage phase is ambiguous. Human Heredity. 2003;55(1):56-65. https://doi.org/10.1159/000071811
Lake, Stephen L. ; Lyon, H. ; Tantisira, K. ; Silverman, E. K. ; Weiss, S. T. ; Laird, N. M. ; Schaid, Daniel J. / Estimation and tests of haplotype-environment interaction when linkage phase is ambiguous. In: Human Heredity. 2003 ; Vol. 55, No. 1. pp. 56-65.
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