Genetic control of the HDL proteome

Nathalie Pamir; Calvin Pan; Deanna L. Plubell; Patrick M. Hutchins; Chongren Tang; Jake Wimberger; Angela Irwin; Thomas Q. de Aguiar Vallim; Jay W. Heinecke; Aldons J. Lusis

We have attempted to identify distal (trans-acting) factors affecting HDL protein levels (Supplemental Table 2 ). In contrast to local eQTL, where only SNPs within 1Mb of the gene are tested for association, distal QTL analyses involve genome wide SNP tests for association, requiring a much higher threshold for significance. A number of the likely significant distal eQTL occur with several Mb of the gene and, thus, probably result from either long range (>1 Mb) linkage disequilibrium or chromosome looping interactions (for example Apoh, Apom, B2m, H2-Q10, and Pp1c) (Supplemental Table 2 ). The pQTL analysis also identified some highly significant distal (trans-acting) interactions, most notably for Apoa2 (p=4.6 x 10 -14 ). The Apoa2 locus is about 5 Mb from the structural gene and the significant association is probably the result of linkage disequilibrium or chromosome looping.