Linkage disequilibrium across two different single-nucleotide polymorphism genome scans

Abstract

Linkage disequilibrium (LD) content was calculated for the Genetic Analysis Workshop 14 Affymetrix and Illumina single-nucleotide polymorphism (SNP) genome scans of the Collaborative Study on the Genetics of Alcoholism samples. Pair-wise LD was measured as both D' and r2 on 505 pedigree founder individuals. The r2 estimates were then used to correct the multipoint identity by descent matrix (MIBD) calculation to account for LD and LOD scores on chromosomes 3 and 18 were calculated for COGA's ttdt3 electrophysiological trait using those MIBDs. Extensive LD was observed throughout both marker sets, and it was higher in Affymetrix's more dense SNP map. However, SNP density did not solely account for Affymetrix's higher LD. MIBD estimation procedures assume linkage equilibrium to construct genotypes of non-genotyped pedigree founder individuals, and dense SNP genotyping maps are likely to contain moderate to high LD between markers. LOD score plots calculated after correction for LD followed the same general pattern as uncorrected ones. Since in our study almost half of the pedigree founders were genotyped, it is possible that LD had a minor impact on the LOD scores. Caution should probably be taken when using high density SNP maps when many non-genotyped founders are present in the study pedigrees.

Figure 1

LD frequency across Affymetrix and Illumina SNP maps. LD frequency distribution of Affymetrix (blue/black bars) and Illumina (green/gray bars) SNP maps, as measured by r² (left) and |D'| (right). Bar names are the LD category boundaries. Note "U" shaped distribution of the LD content of Affymetrix map, and the general increase of LD, when measured as |D'|.

Figure 2

LOD scores obtained using MIBDs uncorrected and corrected for LD. These are plots of the maximum LOD score region of chromosomes 3 and 18 of the COGA ttdt3 trait. LOD scores were calculated using MIBDs constructed by removing SNP pairs that in founders showed LD as r² ≥ {0.2, 0.4, 0.6}. LOD scores calculated using uncorrected MIBDs are also shown.