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In these studies, expression levels are viewed as quantitative traits, and gene expression phenotypes are mapped to particular genomic loci by combining studies of variation in gene expression patterns with genome-wide genotyping. In fact, it is difficult to identify regulatory regions in the genome, let alone to predict how polymorphisms in regulatory regions affect gene expression levels temporally or spatially Genome-scale eQTL mapping studies in nonhuman organisms have predominantly focused on three objectives: (i) to identify QTLs associated with variation in transcript abundances in defined mapping populations and categorize them as proximal or distal to the locus of the transcript they affect, (ii) to determine the numbers, genomic distributions and magnitudes of eQTL effects on transcript levels and (iii) to evaluate whether eQTLs interact additively to control transcript levels. One can view eQTL mapping as a sort of large-scale mutagenesis experiment, in which •10 million common single nucleotide polymorphisms (SNPs) have been sprinkled down on the human genome, and each individual receives a random collection of these trans-eQTL quantita’ di mRNA cis-eQTL ChIP-seq ChIP-seq Gene expression differs among individuals and populations and is thought to be a major determinant of phenotypic variation. Although variation and genetic loci responsible for RNA expression levels have been analysed extensively in human populations1, 2, 3, 4, 5, our knowledge is limited regarding the differences in human protein abundance and the genetic basis for this difference. Variation in messenger RNA expression is not a perfect surrogate for protein expression because the latter is influenced by an array of posttranscriptional regulatory mechanisms, and, empirically, the correlation between protein and mRNA levels is generally modest6, 7. Here we used isobaric tag-based quantitative mass spectrometry to determine relative protein levels of 5,953 genes in lymphoblastoid cell lines from 95 diverse individuals genotyped in the HapMap Project8, 9. We found that protein levels are heritable molecular phenotypes that exhibit considerable variation between individuals, populations and sexes. Levels of specific sets of proteins involved in the same biological process covary among individuals, indicating that these processes are tightly regulated at the protein level. We identified cis-pQTLs (protein quantitative trait loci), including variants not detected by previous transcriptome studies. This study demonstrates the feasibility of high-throughput human proteome quantification that, when integrated with DNA variation and transcriptome information, adds a new dimension to the characterization of gene expression regulation.