Document Detail


Simultaneously correcting for population stratification and for genotyping error in case-control association studies.
MedLine Citation:
PMID:  17846998     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In population-based case-control association studies, the regular chi (2) 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 2x3 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.
Authors:
K F Cheng; W J Lin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-08-22
Journal Detail:
Title:  American journal of human genetics     Volume:  81     ISSN:  0002-9297     ISO Abbreviation:  Am. J. Hum. Genet.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-09-11     Completed Date:  2007-10-30     Revised Date:  2010-09-15    
Medline Journal Info:
Nlm Unique ID:  0370475     Medline TA:  Am J Hum Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  726-43     Citation Subset:  IM    
Affiliation:
Biostatistics Center and Department of Public Health, China Medical University, Taiwan, China. kfcheng@mail.cmu.esu.tw
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MeSH Terms
Descriptor/Qualifier:
Alleles
Bayes Theorem
Bias (Epidemiology)
Case-Control Studies
Genetic Predisposition to Disease*
Genetic Techniques*
Genetics, Population*
Genotype
Humans
Models, Genetic
Models, Statistical
Sample Size
Comments/Corrections

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