Format

Send to:

Choose Destination
See comment in PubMed Commons below
Genet Epidemiol. 2002 Oct;23(3):221-33.

On the advantage of haplotype analysis in the presence of multiple disease susceptibility alleles.

Author information

  • 1Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709-2233, USA. morrisr@niehs.nih.gov

Abstract

We investigated the effect of multiple susceptibility alleles at a single disease locus on the statistical power of a likelihood ratio test to detect association between alleles at a marker locus and a disease phenotype in a case-control design. Using simplifying assumptions to obtain the joint frequency distribution of marker and disease locus alleles, we present numerical results that illustrate the impact of historical variation of initial associations between marker alleles and susceptibility alleles on the power of a likelihood ratio test for association. Our results show that an increase in the number of susceptibility alleles produces a decrease in power of the likelihood ratio test. The decrease in power in the presence of multiple susceptibility alleles, however, is less for markers with multiple alleles than for markers with two alleles. We investigate the implications of this observation for tests of association based on haplotypes made up of tightly linked single-nucleotide polymorphisms (SNPs). Our results suggest that an analysis based on haplotypes can be advantageous over an analysis based on individual SNPs in the presence of multiple susceptibility alleles, particularly when linkage disequilibria between SNPs is weak. The results provide motivation for further development of statistical methods based on haplotypes for assessing the potential for association methods to identify and locate complex disease genes.

Copyright 2002 Wiley-Liss, Inc.

PMID:
12384975
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley
    Loading ...
    Write to the Help Desk