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 identified HDL proteome and HDL function for each strain. Using quantitative trait locus (QTL) analyses, we performed genetic mapping. First, associations between SNPs and HDL protein levels and function were determined. Second, the effects of SNPs on gene regulation were determined by eQTL analysis using hepatic and adipose tissue-specific gene expression. Based on the genetic variation in HDL observed, we were able to identify numerous genetic factors mediating HDL composition and provide an approximation of the nature of the interactions between the proteins. Finally, we used protein-protein interaction cluster analyses to build an HDL model that describes the group of proteins that constitute the core proteins and the ones that are peripheral. We identified moderate QTLs associated with HDLs sterol efflux capacity. Our results reveal a great deal of heterogeneity and inter-correlation, some of which is of proteins that are acutely regulated by the environment (ie. Diet and inflammationhttp://homepages.uc.edu/~davidswm/HDLproteome.html). The H2 scores for such proteins are expected to be zero. Furthermore, due to our study design, the proteins that are strain specific are also expected to have a H2 of zero.