Cited by 369Genetic Associations and EpidemiologyForensic and Genetic ResearchGenetic Mapping and Diversity in Plants and Animals

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

Morris, Richard W., Kaplan, Norman L.·2002·Genetic Epidemiology

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.

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Crossref · 10.1002/gepi.10200

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  • Haplotype analysis can increase the statistical power of genetic analysis and identify key disease-associated SNPs or haplotypes.

    “Compared to SNP-based studies, haplotype analysis can increase the statistical power of genetic analysis and identify key disease-associated SNPs or haplotypes [46].”

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Authors
Morris, R. W., & Kaplan, N. L.
Affiliations
National Institutes of Health (US)
Corresponding author
Morris, Richard W.
Venue
Genetic Epidemiology
Publisher
Wiley
Published
2002-10
Volume
23
Issue
3
Pages
221-233
ISSN
  • 0741-0395 (ISSN-L)
  • 1098-2272
OpenAlex
W2029361834
Cited by
369
References
24
Citations by year
2026: 2 · 2025: 4 · 2024: 7 · 2023: 7 · 2022: 8 · 2021: 3 · 2020: 8 · 2019: 23 · 2018: 11 · 2017: 8 · 2016: 15 · 2015: 17 · 2014: 21 · 2013: 16 · 2012: 18
FWCI
10.96
Type
journal article
Language
en
Open access
closed
Locations
  • Genetic Epidemiology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
Keywords
haplotype analysis, statistical power, likelihood ratio test, genetic association testing, case-control study, linkage disequilibrium, single nucleotide polymorphisms, marker alleles
MeSH terms
Alleles, Chromosome Mapping, Gene Frequency, Genetic Markers, Genetic Testing, Haplotypes, Humans, Reproducibility of Results, Linkage Disequilibrium, Likelihood Functions, Case-Control Studies, Risk Assessment, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genetic Diseases, Inborn

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