An application of the latent p value method to assess linkage in asthma pedigrees.
OBJECTIVE
The latent p value is a recently proposed empirical method for assessing evidence against a null hypothesis in a stochastic system involving latent, unobservable variables. It is particularly applicable to genome-wide genetic linkage analysis for test statistics with poorly defined analytical distributions.


METHODS
We describe an implementation of the latent p value method and its application to a linkage analysis of asthma in 81 extended pedigrees containing 1,858 people genotyped at 533 microsatellite markers. We compare the performance of the latent p value method to a more conventional p value calculation. We also compare the performance of various linkage statistics within this pedigree resource.


RESULTS
Using a novel linkage score referred to as the C-link statistic, our analysis provides strong evidence for a recessive gene influencing asthma on chromosome 5q13 (median latent p value = 0.03). We also demonstrate remarkable improvement in computational requirements compared to a more conventional empirical p value calculation.


CONCLUSIONS
The latent p value method is indeed feasible and provides a computationally efficient means to evaluate evidence for linkage regardless of the choice of linkage statistic.
Teerlink
Craig C
CC
Department of Internal Medicine, University of Utah School of Medicine, University of Utah, Salt Lake City, Utah 84108-1266, USA. craig.teerlink @ utah.edu
Thomas
Alun
A
D000818:Animals; D001249:Asthma / Q000235:genetics*; D008040:Genetic Linkage; D018895:Microsatellite Repeats / Q000235:genetics; D010375:Pedigree