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. 2010 Apr;34(3):201-12.
doi: 10.1002/gepi.20448.

Comparisons of multi-marker association methods to detect association between a candidate region and disease

David H Ballard  1 , Judy Cho, Hongyu Zhao
Affiliations

Comparisons of multi-marker association methods to detect association between a candidate region and disease

David H Ballard et al. Genet Epidemiol. 2010 Apr.

Abstract

The joint use of information from multiple markers may be more effective to reveal association between a genomic region and a trait than single marker analysis. In this article, we compare the performance of seven multi-marker methods. These methods include (1) single marker analysis (either the best-scoring single nucleotide polymorphism in a candidate region or a combined test based on Fisher's method); (2) fixed effects regression models where the predictors are either the observed genotypes in the region, principal components that explain a proportion of the genetic variation, or predictors based on Fourier transformation for the genotypes; and (3) variance components analysis. In our simulation studies, we consider genetic models where the association is due to one, two, or three markers, and the disease-causing markers have varying allele frequencies. We use information from either all the markers in a region or information only from tagging markers. Our simulation results suggest that when there is one disease-causing variant, the best-scoring marker method is preferred whereas the variance components method and the principal components method work well for more common disease-causing variants. When there is more than one disease-causing variant, the principal components method seems to perform well over all the scenarios studied. When these methods are applied to analyze associations between all the markers in or near a gene and disease status for an inflammatory bowel disease data set, the analysis based on the principal components method leads to biologically more consistent discoveries than other methods.

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Figures

Fig. 1
Fig. 1
Power comparisons of seven multi-locus association methods when the disease causing allele has a frequency of 44% and the disease prevalence is 10%.
Fig. 2
Fig. 2
Power comparisons of seven multi-locus association methods when the disease causing allele has a frequency of 30% and the disease prevalence is 10%.
Fig. 3
Fig. 3
Power comparisons of seven multi-locus association methods when the disease causing allele has a frequency of 2% and the disease prevalence is 10%.
Fig. 4
Fig. 4
The histogram of the minor allele frequency distribution of the SNPs that have been associated with one or more diseases through genome-wide association studies.
See this image and copyright information in PMC

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