Vol. 50, No. 4, 2000
Issue release date: July–August 2000 (April 2000)
Hum Hered 2000;50:211–223
(DOI:10.1159/000022918)
Original Paper
Add to my selection

A Unified Approach to Adjusting Association Tests for Population Admixture with Arbitrary Pedigree Structure and Arbitrary Missing Marker Information

Rabinowitz D.a · Laird N.b
aDepartment of Statistics, Columbia University, New York, N.Y., and bDepartment of Biostatistics, Harvard School of Public Health, Boston, Mass., USA
email Corresponding Author


 goto top of outline Key Words

  • Haplotype relative risk
  • Identity by descent
  • Linkage analysis
  • Linkage disequilibrium
  • Transmission/disequilibrium

 goto top of outline Abstract

A general approach to family-based examinations of association between marker alleles and traits is proposed. The approach is based on computing p values by comparing test statistics for association to their conditional distributions given the minimal sufficient statistic under the null hypothesis for the genetic model, sampling plan and population admixture. The approach can be applied with any test statistic, so any kind of phenotype and multi-allelic markers may be examined, and covariates may be included in analyses. By virtue of the conditioning, the approach results in correct type I error probabilities regardless of population admixture, the true genetic model and the sampling strategy. An algorithm for computing the conditional distributions is described, and the results of the algorithm for configurations of nuclear families are presented. The algorithm is applicable with all pedigree structures and all patterns of missing marker allele information.

Copyright © 2000 S. Karger AG, Basel


 goto top of outline References
  1. Boehnke M, Langefeld CD: Genetic association mapping based on discordant sib pairs: The discordant-alleles test. Am J Hum Genet 1998;62:950–961.
  2. Cleves MA, Olson JM, Jacobs KB: Exact transmission-disequilibrium tests with multiallelic markers. Genet Epidemiol 1997;14:337–347.
  3. Cox DR, Hinkley DV: Theoretical Statistics. New York, Halsted Press, 1974.
  4. Curtis D, Sham PC: A note on the application of the transmission disequilibrium test when a parent is missing. Am J Hum Genet 1995;56:811–812.
  5. Ewens WJ, Spielman RS: The transmission/disequilibrium test: History subdivision, and admixture. Am J Hum Genet 1995;57:455–464.
  6. Falk CT, Rubinstein P: Haplotype relative risks: An easy reliable way to construct a proper control sample for risk calculations. Ann Hum Genet 1987;51:227–233.
  7. Knapp M: The transmission/disequilibrium test and parental-genotype reconstruction: The reconstruction-combined transmission/disequilibrium test. Am J Hum Genet 1999;64:861–870.
  8. Kaplan NL, Martin ER, Weir BS: Power studies for the transmission/disequilibrium tests with multiple alleles. Am J Hum Genet 1997;60:691–702.
  9. Lazzeroni LC, Lange K: A conditional inference framework for extending the transmission/disequilibrium test. Hum Hered 1998;48:67–81.
  10. Martin ER, Kaplan NL, Weir BS: Tests for linkage and association in nuclear families. Am J Hum Genet 1997;61:439–448.
  11. Rabinowitz D: A transmission disequilibrium test for quantitative trait loci. Hum Hered 1997;47:342–350.
  12. Schaid DJ, Li H: Genotype relative-risks and association tests for nuclear families with missing parental data. Genet Epidemiol 1997;14:1113–1118.
  13. Spielman RS, Ewens WJ: A sib-ship test for linkage in the presence of association: The sib transmission/disequilibrium test. Am J Hum Genet 1998;62:450–458.
  14. Spielman RS, McGinnis RE, Ewens WJ: Transmission test for linkage disequilibrium: The insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet 1993;52:506–516.
  15. Terwilliger JD, Ott J: A haplotype-based ‘haplotype relative risk’ approach to detecting allelic associations. Hum Hered 1992;42:337–346.

 goto top of outline Author Contacts

Daniel Rabinowitz
Department of Statistics, Mathematics Building, Mail Code 4403
Columbia University, Broadway and 120th St.
New York, NY 10027 (USA)
Tel. +1 212 854 3400, Fax +1 232 663 2454, E-Mail dan@stat.columbia.edu


 goto top of outline Article Information

Received: Received: February 2, 1999
Revision received: March 23, 1999
Accepted: April 1, 1999
Number of Print Pages : 13
Number of Figures : 1, Number of Tables : 10, Number of References : 15


 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. 50, No. 4, Year 2000 (Cover Date: July-August 2000 (Released April 2000))

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

For additional information: http://www.karger.ch/journals/hhe


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.