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.
Original language | English |
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Journal | Human Heredity |
Volume | 72 |
Issue number | 3 |
Pages (from-to) | 153-160 |
Number of pages | 8 |
ISSN | 0001-5652 |
DOIs | |
Publication status | Published - 2011 |
Externally published | Yes |
Keywords
- Case-control
- Misclassification
- Power
- Sequencing data