Assessing the impact of non-differential genotyping errors on rare variant tests of association

Hum Hered. 2011;72(3):153-60. doi: 10.1159/000332222. Epub 2011 Oct 15.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Genetic Association Studies / methods*
  • Genotyping Techniques / methods*
  • Heterozygote
  • Homozygote
  • Humans
  • Models, Genetic
  • Mutation / genetics*
  • Regression Analysis
  • Research Design