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Jackknife-based gene-gene interaction tests for untyped SNPs

Authors
Song, MS (Song, Minsun)
Issue Date
Jul-2015
Publisher
BIOMED CENTRAL LTD
Citation
BMC GENETICS, v.16, no.1
Journal Title
BMC GENETICS
Volume
16
Number
1
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/147150
DOI
10.1186/s12863-015-0225-9
ISSN
1471-2156
Abstract
Background: Testing gene-gene interaction in genome-wide association studies generally yields lower power than testing marginal association. Meta-analysis that combines different genotyping platforms is one method used to increase power when assessing gene-gene interactions, which requires a test for interaction on untyped SNPs. However, to date, formal statistical tests for gene-gene interaction on untyped SNPs have not been thoroughly addressed. The key concern for gene-gene interaction testing on untyped SNPs located on different chromosomes is that the pair of genes might not be independent and the current generation of imputation methods provides imputed genotypes at the marginal accuracy. Results: In this study we address this challenge and describe a novel method for testing gene-gene interaction on marginally imputed values of untyped SNPs. We show that our novel Wald-type test statistics for interactions with and without constraints in the interaction parameters follow the asymptotic distributions which are the same as those of the corresponding tests for typed SNPs. Through simulations, we show that the proposed tests properly control type I error and are more powerful than the extension of the classical dosage method to interaction tests. The increase in power results from a proper correction for the
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