Combined use of GWAS and eQTL information to identify genes controlling platelet biology

Genome Wide Association Studies (GWAS) have identified at least 68 loci involved in megakaryopoiesis and platelet formation. As for all GWAS, identified risk loci span hundreds of kilobases encompassing multiple genes, such that causative variants and genes remain largely unknown. To aid in the identification of causative genes underlying GWAS hits for platelet function (as well as other phenotypes including common complex diseases), we have generated a dataset (" CEDAR ") comprising genome-wide SNP and transcriptome data on nine primary cell types, including platelets, for 330 healthy Caucasian individuals. In addition, we have measured platelet counts and volume, as well as platelet reactivity to ADP, collagen and thrombin-related peptide for all these individuals. After extensive quality control, the ensuing data set has been used to identify (i) QTL influencing platelet count, volume and reactivity, and (ii) cis-and transacting eQTL operating in platelets. To aid in the identification of genes underlying platelet biology, we are applying a recently developed method to search for correlations between association patterns with platelet phenotypes and eQTL association patterns. Such findings would strongly incriminate the corresponding genes (affected by the eQTL) as being causally involved in determining the cognate platelet phenotype. Latest results will be presented.