Hum Hered 2003;56:18–31

Detecting Disease Associations due to Linkage Disequilibrium Using Haplotype Tags: A Class of Tests and the Determinants of Statistical Power

Chapman J.M. · Cooper J.D. · Todd J.A. · Clayton D.G.
JDRF/WT Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
email Corresponding Author

 goto top of outline Key Words

  • htSNPs
  • Association studies
  • Linkage disequilibrium
  • Multi-locus TDT
  • Power

 goto top of outline Abstract

In the ‘indirect’ method of detecting genetic associations between a trait and a DNA variant, we type several markers in a gene or chromosome region of linkage disequilibrium. If there is association between markers and the trait, we presume the existence of one or more causal polymorphisms in the region. In order to obtain a sufficiently dense set of markers it will almost always be necessary to use single nucleotide polymorphisms (SNPs). Although there is an emerging literature on methods for choosing an optimal set of ‘haplotype tag SNPs’ (htSNPs) to detect association between a genetic region and a trait, less attention has been given to the problem of how such studies should be analysed when completed, and how the initial data which was used to select the htSNPs should be incorporated into the analysis. This paper discusses this problem for both population – and family-based association studies. The role of the R2 measure of association between a causal locus and various methods of scoring of marker haplotypes is highlighted. In most cases, the simplest method of scoring (locus coding), which does not require phase resolution, is shown generally to be more powerful than scoring methods that include haplotype information. A new ‘multi-locus TDT’ is also proposed.

Copyright © 2003 S. Karger AG, Basel

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 goto top of outline Author Contacts

David G. Clayton
JDRF/WT Diabetes and Inflammation Laboratory
Cambridge Institute for Medical Research, University of Cambridge
Cambridge, CB2 2XY (UK)
Tel. +44 1223 762669, Fax +44 1223 762640, E-Mail

 goto top of outline Article Information

Received: May 23, 2003
Accepted after revision: August 4, 2003
Number of Print Pages : 14
Number of Figures : 4, Number of Tables : 1, Number of References : 22

 goto top of outline Publication Details

Human Heredity (International Journal of Human and Medical Genetics)
Founded 1950 as Acta Genetica et Statistica Medica by Gunnar Dahlberg; Continued by M. Hauge (1965–1983)

Vol. 56, No. 1-3, Year 2003 (Cover Date: Released November 2003)

Journal Editor: J. Ott, New York, N.Y.
ISSN: 0001–5652 (print), 1423–0062 (Online)

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