A tournament of linkage tests in complex inheritance

The performance of some weakly parametric linkage tests in common use was c ompared on 200 replicates of oligogenic inheritance from Genetic Analysis W orkshop 10. Each random sample for the quantitative trait was dichotomized at different thresholds and also selected through 2 affected sibs, generati ng 8 combinations of sample and variable. The variance component program SO LAR performed best with a continuous trait, even in selected samples, when the population mean was used. The sib-pair program SIBPAL2 was best in most other cases when the phenotype product, population mean, and empirical est imates of pair correlations were used. The BETA program that introduced phe notype products was slightly more powerful than maximum likelihood scores u nder the null hypothesis and approached but did not exceed SIBPAL2 under it s optimal conditions. Type I errors generally exceeded expectations from a chi (2) test, but were conservative with respect to bounds on lods. All met hods can be improved by use of the population mean, empirical correlations, logistic representation for affection status, and correct lods for samples that favour the null hypothesis. It remains uncertain whether all informat ion can be extracted by weakly parametric methods and whether correction fo r ascertainment bias demands a strongly parametric model. Performance on a standard set of simulated data is indispensable for recognising optimal met hods. Copyright (C) 2001 S. Karger AG, Basel.