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Updated: Jun 17, 2026
10:17
An Allele-specific Gene Expression Assay to Test the Functional Basis of Genetic Associations
Published on: November 3, 2010
Armitage's trend test for genome-wide association analysis: one-sided or two-sided?
Yixin Fang1, Yuanjia Wang, Nanshi Sha
1Department of Mathematics and Statistics, Georgia State University, 750 COE, 7th Floor, 30 Pryor Street, Atlanta, Georgia 30303, USA. matyxf@langate.gsu.edu.
BMC Proceedings
|December 19, 2009
Summary
Population stratification confounds genome-wide association studies. Armitage's trend test, using one-sided or two-sided hypotheses, identified significant rheumatoid arthritis SNPs, with one-sided tests aligning with combined sample results.
Area of Science:
- Genetics
- Epidemiology
- Statistical Genetics
Background:
- Population stratification is a key confounder in genome-wide association studies (GWAS) using case-control designs.
- Armitage's trend test and related methods offer partial correction for population stratification.
- The choice between one-sided and two-sided alternative hypotheses in these tests warrants further investigation.
Purpose of the Study:
- To evaluate the utility of one-sided versus two-sided alternative hypotheses in Armitage's trend test for identifying genetic associations.
- To assess the impact of population stratification on rheumatoid arthritis genetic association findings.
- To compare results from individual hypothesis tests with those from combined sample analyses.
Main Methods:
- Utilized Armitage's trend test on single-nucleotide polymorphisms (SNPs) from chromosome 9, focusing on the TRAF1-C5 locus.
- Applied both one-sided and two-sided alternative hypotheses to analyze the dataset from Genetic Analysis Workshop 16.
- Compared findings with results from a combined sample of the North American Rheumatoid Arthritis Consortium (NARAC) and the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA).
Main Results:
- The two-sided hypothesis identified significant associations for SNPs rs12380341 and rs872863, and six other SNPs in the TRAF1-C5 locus.
- The one-sided hypothesis (minor allele positively associated with disease) revealed significant associations only for the six TRAF1-C5 locus SNPs.
- Results from the one-sided hypothesis testing were consistent with the combined NARAC/EIRA sample findings.
Conclusions:
- The choice of hypothesis testing (one-sided vs. two-sided) impacts the identification of significant SNPs in genome-wide association studies.
- One-sided hypothesis testing, specifically for a positive association of the minor allele, provided results consistent with combined population data for rheumatoid arthritis.
- Armitage's trend test is a valuable tool for addressing population stratification in genetic association studies, with careful consideration of hypothesis formulation.
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