title: Variation and genetic control of protein abundance in humans.
abstract: 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 populations, 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 post-transcriptional regulatory mechanisms, and, empirically, the correlation between protein and mRNA levels is generally modest. 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 Project. 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.
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Linfeng
authors.initials: L
authors.lastname: Wu
authors.forename: Sophie I
authors.initials: SI
authors.lastname: Candille
authors.forename: Yoonha
authors.initials: Y
authors.lastname: Choi
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
authors.forename: Lihua
authors.initials: L
authors.lastname: Jiang
authors.forename: Jennifer
authors.initials: J
authors.lastname: Li-Pook-Than
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
authors.forename: Michael
authors.initials: M
authors.lastname: Snyder
mesh_terms: D002460:Cell Line; D005006:Ethnicity / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D060148:HapMap Project; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D010641:Phenotype; D014176:Protein Biosynthesis; D020543:Proteome / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics*; D040901:Proteomics; D040641:Quantitative Trait Loci; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D059467:Transcriptome
chemical_list: D020543:Proteome; D012333:RNA, Messenger