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Haplotype sharing correlation analysis using family data: A comparison with family‐based association test in the presence of allelic heterogeneity
Author(s) -
Qian Dajun
Publication year - 2004
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.20005
Subject(s) - linkage disequilibrium , haplotype , allele , locus (genetics) , genetics , biology , allelic heterogeneity , type i and type ii errors , correlation , genetic association , statistics , genotype , gene , single nucleotide polymorphism , mathematics , geometry
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. © 2004 Wiley‐Liss, Inc.