Original Paper

Backward Haplotype Transmission Association (BHTA) Algorithm - A Fast Multiple-Marker Screening Method
Shaw-Hwa Lo, Tian Zheng

Department of Statistics, Columbia University, New York, N.Y., USA

Address of Corresponding Author

Hum Hered 2002;53:197-215 (DOI: 10.1159/000066194)

  Key Words

• Haplotype
• Transmission disequilibrium
• Screening
• Complex traits
• Epistatic loci
• Marker selection
• Genome scan

  Abstract

The mapping of complex traits is one of the most important and central areas of human genetics today. Recent attention has been focused on genome scans using a large number of marker loci. Because complex traits are typically caused by multiple genes, the common approaches of mapping them by testing markers one after another fail to capture the substantial information of interactions among disease loci. Here we propose a backward haplotype transmission association (BHTA) algorithm to address this problem. The algorithm can administer a screening on any disease model when case-parent trio data are available. It identifies the important subset of an original larger marker set by eliminating the markers of least significance, one at a time, after a complete evaluation of its importance. In contrast with the existing methods, three major advantages emerge from this approach. First, it can be applied flexibly to arbitrary markers, regardless of their locations. Second, it takes into account haplotype information; it is more powerful in detecting the multifactorial traits in the presence of haplotypic association. Finally, the proposed method can potentially prove to be more efficient in future genomewide scans, in terms of greater accuracy of gene detection and substantially reduced number of tests required in scans. We illustrate the performance of the algorithm with several examples, including one real data set with 31 markers for a study on the Gilles de la Tourette syndrome. Detailed theoretical justifications are also included, which explains why the algorithm is likely to select the 'correct' markers.

Copyright © 2002 S. Karger AG, Basel

  Author Contacts

Shaw-Hwa Lo, PhD
Department of Statistics, Columbia University
Mail Code 4403
2990 Broadway, New York, NY 10027 (USA)
Tel. +1 212 854 3639, Fax +1 212 663 2454, E-Mail slo@stat.columbia.edu

  Article Information

Received: Received: April 12, 2002
Revision received: June 14, 2002
Accepted: June 17, 2002
Number of Figures : 6, Number of Tables : 4, Number of References : 31