A fine-scale linkage-disequilibrium measure based on length of haplotype sharing

American Journal of Human Genetics
Yan WangSandrine Dudoit

Abstract

High-throughput genotyping technologies for SNPs have enabled the recent completion of the International HapMap Project (phase I), which has stimulated much interest in studying genomewide linkage-disequilibrium (LD) patterns. Conventional LD measures, such as D' and r(2), are two-point measurements, and their relationship with physical distance is highly noisy. We propose a new LD measure, Delta , defined in terms of the correlation coefficient for shared haplotype lengths around two loci, thereby borrowing information from multiple loci. A U-statistic-based estimator of Delta , which takes into consideration the dependence structure of the observed data, is developed and compared with an estimator based on the usual empirical correlation coefficient. Furthermore, we propose methods for inferring LD-decay rates and recombination hotspots on the basis of Delta . The results from coalescent-simulation studies and analysis of HapMap SNP data demonstrate that the proposed estimators of Delta are superior to the two most popular conventional LD measures, in terms of their close relationship with physical distance and recombination rate, their small variability, and their strong robustness to marker-allele frequencies. These merits ...Continue Reading

References

Apr 20, 2001·Proceedings of the National Academy of Sciences of the United States of America·N E MortonA Collins
Jun 19, 2001·American Journal of Human Genetics·J K Pritchard, M Przeworski
Jul 12, 2002·Nature·Elisabeth DawsonIan Dunham
Jul 15, 2003·American Journal of Human Genetics·Eric C Anderson, John Novembre
Dec 20, 2003·Nature·UNKNOWN International HapMap Consortium

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Citations

Feb 28, 2008·PloS One·David A HughesMark Stoneking
Feb 18, 2016·BioMed Research International·Xian-Qing LiuYi-Ping Liu
Feb 13, 2010·Journal of Mathematical Biology·Arindam RoyChoudhury
Feb 26, 2021·Gene·Raísa Santos CoelhoRyan do Santos Costa
Jun 5, 2021·Bioinformatics·Jeremy J YangTudor I Oprea

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