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

Vol. 50, No. 4, 2000

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Original Paper

A Unified Approach to Adjusting Association Tests for Population Admixture with Arbitrary Pedigree Structure and Arbitrary Missing Marker Information
Daniel Rabinowitz^a, Nan Laird^b

^aDepartment of Statistics, Columbia University, New York, N.Y., and
^bDepartment of Biostatistics, Harvard School of Public Health, Boston, Mass., USA

Address of Corresponding Author

Hum Hered 2000;50:211-223 (DOI: 10.1159/000022918)

Key Words

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

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.

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

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

Medline Abstract (ID 10782012)

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