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.