Send to

Choose Destination
Genet Epidemiol. 2005 Sep;29(2):128-40.

Multilocus linkage disequilibrium mapping by the decay of haplotype sharing with samples of related individuals.

Author information

Department of Statistics, University of Chicago, Chicago, Illinois 60637, USA.


We consider the problem of multilocus linkage disequilibrium (LD) mapping of a trait-associated variant from case-control samples in which some individuals may be related. Our method, which we call DHS-R, is an extension of the decay of haplotype sharing (DHS) method of McPeek and Strahs and Strahs and McPeek. The DHS-R method shares the main features of the DHS method: (1) it allows construction of a confidence interval for the location of a trait-associated variant; (2) it allows for missing observations and unphased genotype data, with the uncertainty in the haplotypes taken into account in the analysis; and (3) it allows for heterogeneity, mutation, recombination, and background LD. The main advances of the DHS-R are (1) the ability to include individuals of arbitrary known relationship (including inbreeding) in the case and control samples; (2) an extension to allow partially-phased haplotypes derived from case-parent trio genotype data; and (3) an extension to allow for genotyping error in the model. Our method, which uses a hidden Markov model for likelihood calculation and maximization, has the advantage of being computationally feasible even in a large, complex pedigree. Simulations based on a 13-generation, 1,623-member Hutterite pedigree demonstrate accurate coverage of the confidence intervals for location of the variant. We apply the method to fine-mapping of a susceptibility locus for bronchial hyperresponsiveness (BHR) in the Hutterites. The results confirm the importance of taking into account the relatedness of individuals in LD mapping.

[Indexed for MEDLINE]

Supplemental Content

Loading ...
Support Center