Weighted Pairwise Correlation and Transmission Disequilibrium
in a Common Oligogenic Disease
E.H. Corder
Center for Demographic Studies, Duke University,
Durham, North Carolina 27710, USA.
Genetic Epidemiology ,
12, 747-751 (1995)
Abstract
Weighted pairwise correlation (WPC) linkage analysis and the transmission
disequilibrium test (TDT) for allelic association were applied to simulated family data for a
common oligogenic disorder in order to localize genes that increase levels of Q1. Preliminary
linear models indicated that Q1 increases with age, Q2, Q3, and the occurrence of D5G28
allele 3 (D5G28(3). WPC provided evidence for linkage of Q1 to Major Gene 1, D5G28 (p <
0.0001), and to other loci when ranks based on age and affection status (Q1 < or > 87.5) were
used to define the phenotype. D5G28 was the only locus linked to Q1 (p = 0.01) when the
phenotype was defined as Q1 adjusted for age, Q2, Q3, and D5G28(3). The TDT indicated
linkage disequilibrium between a gene for elevated Q1 (> 87.5) and alleles at loci adjacent to
D5G28: D5G29(2) was apparently protective (p = 0.008) while allele 8 was associated with risk
(p = 0.007); D5G30(7) was also apparently protective (p = 0.02). However, significant
disequilibrium was not found for D5G28(3), possibly due to lack of adjustment of Q1 and
small sample size. These results imply that the combined use of WPC and the TDT may be
an effective strategy for genomic screens in complex disorders defined by quantitative traits,
especially when the trait can be adjusted for age and other relevant factors.
Association Studies