title: Assessing the impact of non-differential genotyping errors on rare variant tests of association.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Statistics and Operations Research, University of North Carolina, Chapel Hill, NC, USA.
authors: Scott
authors: S
authors: Powers
authors: Shyam
authors: S
authors: Gopalakrishnan
authors: Nathan
authors: N
authors: Tintle
mesh_terms: D056726:Genetic Association Studies / Q000379:methods*; D060005:Genotyping Techniques / Q000379:methods*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics*; D012044:Regression Analysis; D012107:Research Design