Analysis of single nucleotide polymorphisms in candidate genes using the pedigree disequilibrium test.
The pedigree disequilibrium test (PDT) has been proposed recently as a test for association in general pedigrees [Martin et al., Am J Hum Genet 67:146-54, 2000]. The Genetic Analysis Workshop (GAW) 12 simulated data, with many extended pedigrees, is an example the type of data to which the PDT is ideally suited. In replicate 42 from the general population the PDT correctly identifies candidate genes 1, 2, and 6 as containing single nucleotide polymorphisms (SNPs) that are significantly associated with the disease. We also applied the truncated product method (TPM) [Zaykin et al., Genet Epidemiol, in press] to combine p-values in overlapping windows across the genes. Our results show that the TPM is helpful in identifying significant SNPs as well as removing spurious false positives. Our results indicate that, using the PDT, functional disease-associated SNPs can be successfully identified with a dense map of moderately polymorphic SNPs.
Hardy
S W
SW
Bioinformatics Research Center, North Carolina State University, Raleigh, North Carolina, USA.
Weir
B S
BS
Kaplan
N L
NL
Martin
E R
ER
D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable