How allele frequency and study design affect association test statistics with misrepresentation errors

作者：Escott Price Valentina^*; Ghodsi Mansoureh; Schmidt Karl Michael

来源：Biostatistics, 2014, 15(2): 311-326.

DOI：10.1093/biostatistics/kxt048

• Case-control study
• General association test
• Genomic control
• Genotyping errors
• Non-central chi(2) distribution
• Type-I error

We evaluate the effect of genotyping errors on the type-I error of a general association test based on genotypes, showing that, in the presence of errors in the case and control samples, the test statistic asymptotically follows a scaled non-central chi(2) distribution. We give explicit formulae for the scaling factor and non-centrality parameter for the symmetric allele-based genotyping error model and for additive and recessive disease models. They show how genotyping errors can lead to a significantly higher false-positive rate, growing with sample size, compared with the nominal significance levels. The strength of this effect depends very strongly on the population distribution of the genotype, with a pronounced effect in the case of rare alleles, and a great robustness against error in the case of large minor allele frequency. We also show how these results can be used to correct p-values.

• 出版日期2014-4