WEIGHTED PAIRWISE CORRELATION AND TRANSMISSION DISEQUILIBRIUM IN A COMMON OLIGOGENIC DISEASE

Weighted pairwise correlation (WPC) linkage analysis and the transmiss ion disequilibrium test (TDT) for allelic association were applied to simulated family data for a common oligogenic disorder in order to loc alize genes that increase levels of Q1. Preliminary linear models indi cated 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 G ene 1, D5G28 (p < 0.0001), and to other loci when ranks based on age a nd 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 indi cated linkage disequilibirum between a gene for elevated Q1 (> 87.5) a nd alleles at loci adjacent to D5G28: D5G29(2) was apparently protecti ve (p = 0.008) while allele 8 was associated with risk (p = 0.007); D5 G30(7) was also apparently protective (p = 0.02). However, significant disequilibirum was not found for D5G28(3), possibly due to lack of ad justment of Q1 and small sample size. These results imply that the com bined use of WPC and the TDT may be an effective strategy for genomic screens in complex disorders defined by quantitative traits, especiall y when the trait can be adjusted for age and other relevant factors. ( C) 1995 Wiley-Liss, Inc.