Vol. 61, No. 4, 2006
Issue release date: September 2006
Hum Hered 2006;61:189–199
Original Paper
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The APL Test: Extension to General Nuclear Families and Haplotypes and Examination of Its Robustness

Chung R.-H.a, b · Hauser E.R.b · Martin E.R.b
aBioinformatics Research Center, North Carolina State University, Raleigh, N.C., and bCenter for Human Genetics, Duke University Medical Center, Durham, N.C., USA
email Corresponding Author

 goto top of outline Key Words

  • Family-based association
  • Linkage disequilibrium
  • Haplotype analysis
  • Rare alleles and rare haplotypes
  • Hardy-Weinberg disequilibrium

 goto top of outline Abstract

Objective: The Association in the Presence of Linkage test (APL) is a powerful statistical method that allows for missing parental genotypes in nuclear families. However, in its original form, the statistic does not easily extend to mixed nuclear family structures nor to multiple-marker haplotypes. Furthermore, the robustness of APL in practice has not been examined. Here we present a generalization of the APL model and examination of its robustness under a variety of non-standard scenarios. Methods: The generalization is made possible by incorporating a bootstrap variance estimator instead of the original robust variance estimator. This allows for use of more than two affected siblings. Haplotype analysis was accomplished by combining estimation of haplotype phase into the EM algorithm. Computer simulation was used to examine robustness of the APL to departures from test assumptions. Results: The extended APL tests both single-marker and multiple-marker haplotypes and shows more power than other association methods. Simulation results showed that the single-marker APL test is robust to the departure from HWE. For the haplotype test, violation of the HWE assumption can inflate type I error. We also evaluated general guidelines for the validity of APL with rare alleles and rare haplotypes. Software for the APL test is available from http://www.chg.duke.edu/research/apl.html.

Copyright © 2006 S. Karger AG, Basel

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    External Resources

 goto top of outline Author Contacts

Eden R. Martin, PhD
Duke University Medical Center, Box 3468
Durham, NC 27710 (USA)
Tel. +1 919 684 0601, Fax +1 919 684 0915
E-Mail emartin@chg.duhs.duke.edu

 goto top of outline Article Information

Received: February 3, 2006
Accepted after revision: May 10, 2006
Published online: July 27, 2006
Number of Print Pages : 11
Number of Figures : 2, Number of Tables : 6, Number of References : 19

 goto top of outline Publication Details

Human Heredity (International Journal of Human and Medical Genetics)

Vol. 61, No. 4, Year 2006 (Cover Date: September 2006)

Journal Editor: Devoto, M. (Philadelphia, Pa.)
ISSN: 0001–5652 (print), 1423–0062 (Online)

For additional information: http://www.karger.com/HHE

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