Article

Haplotype sharing correlation analysis using family data: a comparison with family-based association test in the presence of allelic heterogeneity.

Department of Biostatistics, City of Hope National Medical Center, Duarte, California 91010-3000, USA.
Genetic Epidemiology (impact factor: 3.44). 08/2004; 27(1):43-52. DOI:10.1002/gepi.20005 pp.43-52
Source: PubMed

ABSTRACT The haplotype-sharing correlation (HSC) method for association analysis using family data is revisited by introducing a permutation procedure for estimating region-wise significance at each marker on a study segment. In simulation studies, the HSC method has a correct type 1 error rate in both unstructured and structured populations. The HSC signals on disease segments occur in the vicinity of a true disease locus on a restricted region without recombination hotspots. However, the peak signal may not pinpoint the true disease location in a small region with dense markers. The HSC method is shown to have higher power than single- and multilocus family-based association test (FBAT) methods when the true disease locus is unobserved among the study markers, and especially under conditions of weak linkage disequilibrium and multiple ancestral disease alleles. These simulation results suggest that the HSC method has the capacity to identify true disease-associated segments under allelic heterogeneity that go undetected by the FBAT method that compares allelic or haplotypic frequencies.

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Keywords

association analysis
 
compares allelic
 
family data
 
FBAT method
 
go undetected
 
haplotype-sharing correlation
 
haplotypic frequencies
 
higher power
 
multilocus family-based association test
 
permutation procedure
 
region-wise significance
 
simulation results
 
simulation studies
 
small region
 
study markers
 
study segment
 
true disease location
 
true disease locus
 
true disease-associated segments
 
weak linkage disequilibrium
 

Dajun Qian