NDLI: Simultaneously Correcting for Population Stratification and for Genotyping Error in Case-Control Association Studies

Content Provider	PubMed Central
Author	Cheng, K. F. Lin, W. J.
Copyright Year	2007
Abstract	In population-based case-control association studies, the regular χ2 test is often used to investigate association between a candidate locus and disease. However, it is well known that this test may be biased in the presence of population stratification and/or genotyping error. Unlike some other biases, this bias will not go away with increasing sample size. On the contrary, the false-positive rate will be much larger when the sample size is increased. The usual family-based designs are robust against population stratification, but they are sensitive to genotype error. In this article, we propose a novel method of simultaneously correcting for the bias arising from population stratification and/or for the genotyping error in case-control studies. The appropriate corrections depend on sample odds ratios of the standard 2×3 tables of genotype by case and control from null loci. Therefore, the test is simple to apply. The corrected test is robust against misspecification of the genetic model. If the null hypothesis of no association is rejected, the corrections can be further used to estimate the effect of the genetic factor. We considered a simulation study to investigate the performance of the new method, using parameter values similar to those found in real-data examples. The results show that the corrected test approximately maintains the expected type I error rate under various simulation conditions. It also improves the power of the association test in the presence of population stratification and/or genotyping error. The discrepancy in power between the tests with correction and those without correction tends to be more extreme as the magnitude of the bias becomes larger. Therefore, the bias-correction method proposed in this article should be useful for the genetic analysis of complex traits.
Related Links	http://dx.doi.org/10.1086/520962
Ending Page	743
Page Count	18
Starting Page	726
File Format	PDF
ISSN	00029297
e-ISSN	15376605
Journal	American Journal of Human Genetics
Issue Number	4
Volume Number	81
Language	English
Publisher	American Society of Human Genetics
Publisher Date	2007-10-01
Access Restriction	Open
Rights Holder	American Society of Human Genetics
Subject Keyword	Genetics(clinical) Genetics Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics Genetics (clinical)

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