Multipoint linkage disequilibrium mapping using case-control designs.
Case-control study has been and continues to be one of the most popular designs in epidemiology. More recently, this design has been adopted to test for candidate genes when searching for disease genetic etiology. In this report, we present a multipoint linkage disequilibrium (LD) mapping approach with the focus on estimating the location of the target trait locus. It builds upon a representation, which shows that the difference between a case and a control in probabilities of carrying the target allele of a marker is proportional to that of the trait locus and that the proportionality factor is simply a measure of LD between the trait locus and the marker. Our method has the desired properties that (1) there is no need to specify phases of genotypic data with multiple markers, (2) it provides an estimate of location of the disease locus along with sampling uncertainty to help investigators to narrow chromosomal regions, and (3) a single test statistic is provided to test for LD in the framed region rather than testing the hypothesis one marker at a time. Our simulation work suggests that the proposed method performs well in terms of bias and coverage probability. Extension of the proposed method to account for confounding and genetic heterogeneity is discussed. We apply the proposed method to a published case-control data set for cystic fibrosis.
Liang
Kung-Yee
KY
Division of Biostatistics and Bioinformatics, National Health Research Institutes, Taiwan, R.O.C. kyliang@nhri.org.tw
Chiu
Yen-Feng
YF
D000483:Alleles; D016022:Case-Control Studies; D002874:Chromosome Mapping; D003550:Cystic Fibrosis / Q000235:genetics; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D009154:Mutation