Family-based tests for associating haplotypes with general phenotype data: Application to asthma genetics
Article first published online: 16 DEC 2003
© 2003 Wiley-Liss, Inc.
Volume 26, Issue 1, pages 61–69, January 2004
How to Cite
Horvath, S., Xu, X., Lake, S. L., Silverman, E. K., Weiss, S. T. and Laird, N. M. (2004), Family-based tests for associating haplotypes with general phenotype data: Application to asthma genetics. Genet. Epidemiol., 26: 61–69. doi: 10.1002/gepi.10295
- Issue published online: 16 DEC 2003
- Article first published online: 16 DEC 2003
- Manuscript Accepted: 22 AUG 2003
- Manuscript Received: 23 JUN 2003
- NHLBI. Grant Numbers: N01-HR-16049, SCOR P50 HL67664
- NIH. Grant Number: 2R01MH059532-04A1
- candidate region;
We provide a general purpose family-based testing strategy for associating disease phenotypes with haplotypes when phase may be ambiguous and parental genotype data may be missing. These tests for linkage and association can be used in candidate gene studies with tightly linked markers. Our proposed weighted conditional approach extends the method described in Rabinowitz and Laird [Human Heredity 504:227–233, 2000] to multiple markers. It is attractive because it provides haplotype tests for family-based studies that are efficient and robust to population admixture, phenotype distribution specification, and ascertainment based on phenotypes. It can handle missing parental genotypes and/or missing phase in both offspring and parents. It yields either haplotype-specific (univariate) tests or multi-haplotype (global) tests. This extension has been implemented in the freely available software haplotype FBAT. We used the haplotype FBAT program to test for associations between asthma phenotypes and single nucleotide polymorphisms (SNPs) in the beta-2 adrenergic receptor gene. Whereas no single SNP showed significant association with asthma diagnosis or bronchodilator responsiveness (quantitative trait), a haplotype-based global test found a highly significant association with asthma diagnosis (P value <0.00005) and the measure of bronchodilator responsiveness (P value =0.016). Genet Epidemiol 26:61–69, 2004. © 2003 Wiley-Liss, Inc.