Format

Send to

Choose Destination
Hum Hered. 2010;70(1):23-33. doi: 10.1159/000298326. Epub 2010 Apr 23.

Testing haplotype-environment interactions using case-parent triads.

Author information

1
Biostatistics Branch, NIEHS, NIH, DHHS, Research Triangle Park, NC 27709, USA.

Abstract

OBJECTIVE:

Joint analysis of multiple SNP markers can be informative, but studying joint effects of haplotypes and environmental exposures is challenging. Population structure can involve both genes and exposures and a case-control study is susceptible to bias from either source of stratification. We propose a procedure that uses case-parent triad data and, though not fully robust, resists bias from population structure.

METHODS:

Our procedure assumes that haplotypes under study have no influence on propensity to exposure. Then, under a no-interaction null hypothesis (multiplicative scale), transmission of a causative haplotype from parents to affected offspring might show distortion from Mendelian proportions but should be independent of exposure. We used this insight to develop a permutation test of no haplotype-by-exposure interaction.

RESULTS:

Simulations showed that our proposed test respects the nominal Type I error rate and provides good power under a variety of scenarios. We illustrate by examining whether SNP variants in GSTP1 modify the association between maternal smoking and oral clefting.

CONCLUSION:

Our procedure offers desirable features: no need for haplotype estimation, validity under unspecified genetic main effects, tolerance to Hardy-Weinberg disequilibrium, ability to handle missing genotypes and a relatively large number of SNPs. Simulations suggest resistance to bias due to exposure-related population stratification.

PMID:
20413979
PMCID:
PMC2912643
DOI:
10.1159/000298326
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for S. Karger AG, Basel, Switzerland Icon for PubMed Central
Loading ...
Support Center