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Effect of linkage disequilibrium between markers in linkage and association analyses

Effect of linkage disequilibrium between markers in linkage and association analyses

Authors :
Alun Thomas
Gang Zheng
Kees Albers
Josée Dupuis
Glenys Thomson
Kristina Allen-Brady
Robert C. Elston
Eric Tsung
Kelly Cho
Weihua Zhang
Julie T. Ziegler
Hua Tang
Keyan Zhao
Hilbert J. Kappen
Qiong Yang
Source :
Genetic Epidemiology. 31:S139-S148
Publication Year :
2007
Publisher :
Wiley, 2007.

Abstract

Contributions to Group 17 of the Genetic Analysis Workshop 15 considered dense markers in linkage disequilibrium (LD) in the context of either linkage or association analysis. Three contributions reported on methods for modeling LD or selecting a subset of markers in linkage equilibrium to perform linkage analysis. When all markers were used without modeling LD, inflated evidence for linkage was observed when parental genotypes were missing. All methods for handling LD led to some decreased linkage evidence. Two groups performed a genome-wide association scan using either mixed models to account for known or unknown relatedness between individuals, trend tests or combination statistics. All methods failed to detect four of the eight simulated loci because of low LD in some regions. Three groups performed association analysis using simulated dense markers on chromosome 6, where a simulated HLA-DRB1 locus played a major role in disease susceptibility along with two additional loci of smaller effect. The overall conditional genotype method correctly identified both additional loci while a novel transmission disequilibrium test-statistic to combine studies with non-overlapping markers identified one HLA locus after stratifying on the parental HLA-DRB1 genotypes; LD mapping using the Malecot model mapped two loci in this region, even when using greatly reduced marker density. While LD between markers appears to be a nuisance that may cause spurious linkage results with missing parental genotypes in linkage analysis, association analysis thrives on LD, and disease genes fail to be detected in regions of low LD. Genet. Epidemiol. 31 (Suppl. 1):S139–S148, 2007. © 2007 Wiley-Liss, Inc.

Details

ISSN :
10982272 and 07410395
Volume :
31
Database :
OpenAIRE
Journal :
Genetic Epidemiology
Accession number :
edsair.doi.dedup.....26164b6dbf27106c6d32c8da7a6e6c17
Full Text :
https://doi.org/10.1002/gepi.20291