A tournament of linkage tests in complex inheritance.
The performance of some weakly parametric linkage tests in common use was compared on 200 replicates of oligogenic inheritance from Genetic Analysis Workshop 10. Each random sample for the quantitative trait was dichotomized at different thresholds and also selected through 2 affected sibs, generating 8 combinations of sample and variable. The variance component program SOLAR 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 estimates of pair correlations were used. The BETA program that introduced phenotype products was slightly more powerful than maximum likelihood scores under the null hypothesis and approached but did not exceed SIBPAL2 under its optimal conditions. Type I errors generally exceeded expectations from a chi(2) test, but were conservative with respect to bounds on lods. All methods 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 information can be extracted by weakly parametric methods and whether correction for ascertainment bias demands a strongly parametric model. Performance on a standard set of simulated data is indispensable for recognising optimal methods.
Zhang
W
W
Human Genetics Research Division, University of Southampton, Southampton General Hospital, Duthie Building, Tremona Road, Southampton SO16 6YD, UK. wz@soton.ac.uk
Tapper
W
W
Collins
A
A
Jacobs
K B
KB
Elston
R C
RC
Morton
N E
NE
D000465:Algorithms; D000483:Alleles; D008040:Genetic Linkage; D014644:Genetic Variation; D006801:Humans; D016015:Logistic Models; D015233:Models, Statistical; D010641:Phenotype; D019655:Quantitative Trait, Heritable; D012984:Software