The impact of genotyping error on family-based analysis of quantitative traits

Errors in genotyping can substantially influence the power to detect linkag e using affected sib-pairs, but it is not clear what effect such errors hav e on quantitative trait analyses. Here we use Monte Carlo simulation to exa mine the influence of genotyping error on multipoint vs two-point analysis, variable map density, locus effect size and allele frequency in quantitati ve trait linkage and association studies of sib-pairs. The analyses are con ducted using variance components methods. We contrast the effects of error on quantitative trait analyses with those on the affected sib-pair design. The results indicate that genotyping error influences linkage studies of af fected sib pairs more severely than studies of quantitative traits in unsel ected sibs. In situations of modest effect size, 5% genotyping error elimin ates all supporting evidence for linkage to a true susceptibility locus in affected pairs, but may only result in a loss of 15% of linkage information in random pairs. Multipoint analysis does not suffer substantially more th an two-point analysis; for moderate error rates (<5%), multipoint analysis with error is more powerful than two-point with no error. Map density does not appear to be an important factor for linkage analysis. QTL association analyses of common alleles are reasonably robust to genotyping error but po wer can be affected dramatically with rare alleles.