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.

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

Source Publication Title

Human Heredity

Publisher

Karger

Volume

72

Issue

3

First Page

152

DOI

10.1159/000332222

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