Parent-child pair design for detecting gene-environment interactions in complex diseases

Hum Genet. 2007 Jul;121(6):745-57. doi: 10.1007/s00439-007-0369-4. Epub 2007 May 10.

Abstract

It is becoming clear that the etiology of complex diseases involves not only genetic and environmental factors but also gene-environment (GE) interactions. Therefore, it is important to take account of all these factors to improve the power of an epidemiological study design. We propose here a novel parent-child pair (PCP) design for this purpose. In comparison with conventional designs, this approach has the following advantages: (a) PCP is a 4 x 16 design consisting of pairs of parent-child (PC) genotype statuses, PC exposure statuses and PC disease statuses. Therefore, it utilizes more information than the traditional approaches in association studies; (b) It can determine whether findings in studies of association between disease and genetic or environmental factors and their interaction are spurious, arising from Hardy-Weinberg disequilibrium or the other factors; (c) Since the information from both parents and children of the PC pairs are used in this design, it has high power for detecting association of candidate gene, exposure with a complex disease and GE interaction. We also present a set of estimates of relative risks of candidate genes, exposures and GE interactions under the multiplicative model and a method for computing the sample size requirements to test for these relative risks in the context of the PCP design.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Alleles
  • Biometry
  • Child
  • Disease / etiology*
  • Environment*
  • Epidemiologic Methods*
  • Female
  • Genetic Predisposition to Disease*
  • Genetics, Medical / methods
  • Humans
  • Male
  • Probability
  • Risk Factors
  • Sample Size