Document Type
Article
Publication Date
11-2011
Department
Mathematics, Statistics, and Computer Science
Keywords
sequencing data, power, case-control, misclassification
Abstract
Background/Aims: We aim to quantify the effect of non-differential genotyping errors on the power of rare variant tests and identify those situations when genotyping errors are most harmful. Methods: We simulated genotype and phenotype data for a range of sample sizes, minor allele frequencies, disease relative risks and numbers of rare variants. Genotype errors were then simulated using five different error models covering a wide range of error rates. Results: Even at very low error rates, misclassifying a common homozygote as a heterozygote translates into a substantial loss of power, a result that is exacerbated even further as the minor allele frequency decreases. While the power loss from heterozygote to common homozygote errors tends to be smaller for a given error rate, in practice heterozygote to homozygote errors are more frequent and, thus, will have measurable impact on power. Conclusion: Error rates from genotype-calling technology for next-generation sequencing data suggest that substantial power loss may be seen when applying current rare variant tests of association to called genotypes.
Source Publication Title
Human Heredity
Publisher
Karger
Volume
72
Issue
3
First Page
152
DOI
10.1159/000332222
Recommended Citation
Powers S, Gopalakrishnan S, and Tintle NL. (2011) “Assessing the impact of non-differential genotyping errors on rare variant tests of association” Human Heredity. 72(3):152-159. doi: 10.1002/gepi.20650
Included in
Bioinformatics Commons, Genetics and Genomics Commons, Statistics and Probability Commons
Comments
This is a pre-publication author manuscript of the following final, published article: Powers S, Gopalakrishnan S,and Tintle NL. (2011) “Assessing the impact of non-differential genotyping errors on rare variant tests of association” Human Heredity. 72(3):152-159. doi: 10.1002/gepi.20650
The definitive version is published by Karger and available at http://www.karger.com/?DOI=10.1159/000332222