title: Generalizing Terwilliger's likelihood approach: a new score statistic to test for genetic association.
abstract: BACKGROUND
  In this paper, we propose a one degree of freedom test for association between a candidate gene and a binary trait. This method is a generalization of Terwilliger's likelihood ratio statistic and is especially powerful for the situation of one associated haplotype. As an alternative to the likelihood ratio statistic, we derive a score statistic, which has a tractable expression. For haplotype analysis, we assume that phase is known.
  
  
  RESULTS
  By means of a simulation study, we compare the performance of the score statistic to Pearson's chi-square statistic and the likelihood ratio statistic proposed by Terwilliger. We illustrate the method on three candidate genes studied in the Leiden Thrombophilia Study.
  
  
  CONCLUSIONS
  We conclude that the statistic follows a chi square distribution under the null hypothesis and that the score statistic is more powerful than Terwilliger's likelihood ratio statistic when the associated haplotype has frequency between 0.1 and 0.4 and has a small impact on the studied disorder. With regard to Pearson's chi-square statistic, the score statistic has more power when the associated haplotype has frequency above 0.2 and the number of variants is above five.
authors: Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. rachid.elgalta@organon.com
authors: Rachid
authors: R
authors: el Galta
authors: Shirley
authors: S
authors: Uitte de Willige
authors: Marieke C H
authors: MC
authors: de Visser
authors: Quinta
authors: Q
authors: Helmer
authors: Li
authors: L
authors: Hsu
authors: Jeanine J
authors: JJ
authors: Houwing-Duistermaat
mesh_terms: D016009:Chi-Square Distribution; D003198:Computer Simulation; D005340:Fibrinogen / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D016013:Likelihood Functions; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics*
chemical_list: D005340:Fibrinogen