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Open Access Research article

Genome wide association studies in presence of misclassified binary responses

Shannon Smith1, El Hamidi Hay1, Nourhene Farhat4 and Romdhane Rekaya123*

Author Affiliations

1 Department of Animal and Dairy Science, The University of Georgia, Athens, GA, USA

2 Department of Statistics, The University of Georgia, Athens, GA, USA

3 Institute of Bioinformatics, The University of Georgia, Athens, GA, USA

4 PCOM, Suwanee, Athens, GA, USA

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BMC Genetics 2013, 14:124  doi:10.1186/1471-2156-14-124

Published: 26 December 2013



Misclassification has been shown to have a high prevalence in binary responses in both livestock and human populations. Leaving these errors uncorrected before analyses will have a negative impact on the overall goal of genome-wide association studies (GWAS) including reducing predictive power. A liability threshold model that contemplates misclassification was developed to assess the effects of mis-diagnostic errors on GWAS. Four simulated scenarios of case–control datasets were generated. Each dataset consisted of 2000 individuals and was analyzed with varying odds ratios of the influential SNPs and misclassification rates of 5% and 10%.


Analyses of binary responses subject to misclassification resulted in underestimation of influential SNPs and failed to estimate the true magnitude and direction of the effects. Once the misclassification algorithm was applied there was a 12% to 29% increase in accuracy, and a substantial reduction in bias. The proposed method was able to capture the majority of the most significant SNPs that were not identified in the analysis of the misclassified data. In fact, in one of the simulation scenarios, 33% of the influential SNPs were not identified using the misclassified data, compared with the analysis using the data without misclassification. However, using the proposed method, only 13% were not identified. Furthermore, the proposed method was able to identify with high probability a large portion of the truly misclassified observations.


The proposed model provides a statistical tool to correct or at least attenuate the negative effects of misclassified binary responses in GWAS. Across different levels of misclassification probability as well as odds ratios of significant SNPs, the model proved to be robust. In fact, SNP effects, and misclassification probability were accurately estimated and the truly misclassified observations were identified with high probabilities compared to non-misclassified responses. This study was limited to situations where the misclassification probability was assumed to be the same in cases and controls which is not always the case based on real human disease data. Thus, it is of interest to evaluate the performance of the proposed model in that situation which is the current focus of our research.

Misclassification; Genome wide association; Discrete responses