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

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

DOI 10.1002/gepi.10200

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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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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
DOI: 10.1002/gepi.10200
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
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 14 d)
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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On the advantage of haplotype analysis in the presence of multiple disease susceptibility alleles

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