Effect of genotyping error on type-I error rate of affected sib pair studies with genotyped parents

OBJECTIVE: In affected sib pair studies without genotyped parents the effect of genotyping error is generally to reduce the type I error rate and power of tests for linkage. The effect of genotyping error when parents have been genotyped is unknown. We investigated the type I error rate of the single-point Mean test for studies in which genotypes of both parents are available. METHODS: Datasets were simulated assuming no linkage and one of five models for genotyping error. In each dataset, Mendelian-inconsistent families were either excluded or regenotyped, and then the Mean test applied. RESULTS: We found that genotyping errors lead to an inflated type I error rate when inconsistent families are excluded. Depending on the genotyping-error model assumed, regenotyping inconsistent families has one of several effects. It may produce the same type I error rate as if inconsistent families are excluded; it may reduce the type I error, but still leave an anti-conservative test; or it may give a conservative test. Departures of the type I error rate from its nominal level increase with both the genotyping error rate and sample size. CONCLUSION: We recommend that markers with high error rates either be excluded from the analysis or be regenotyped in all families.