title: Discovery of expression QTLs using large-scale transcriptional profiling in human lymphocytes.
abstract: Quantitative differences in gene expression are thought to contribute to phenotypic differences between individuals. We generated genome-wide transcriptional profiles of lymphocyte samples from 1,240 participants in the San Antonio Family Heart Study. The expression levels of 85% of the 19,648 detected autosomal transcripts were significantly heritable. Linkage analysis uncovered >1,000 cis-regulated transcripts at a false discovery rate of 5% and showed that the expression quantitative trait loci with the most significant linkage evidence are often located at the structural locus of a given transcript. To highlight the usefulness of this much-enlarged map of cis-regulated transcripts for the discovery of genes that influence complex traits in humans, as an example we selected high-density lipoprotein cholesterol concentration as a phenotype of clinical importance, and identified the cis-regulated vanin 1 (VNN1) gene as harboring sequence variants that influence high-density lipoprotein cholesterol concentrations.
authors.affiliation: Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas 78245, USA. hgoring@sfbrgenetics.org
authors.forename: Harald H H
authors.initials: HH
authors.lastname: Göring
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Curran
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Johnson
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Dyer
authors.forename: Jac
authors.initials: J
authors.lastname: Charlesworth
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Cole
authors.forename: Jeremy B M
authors.initials: JB
authors.lastname: Jowett
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Abraham
authors.forename: David L
authors.initials: DL
authors.lastname: Rainwater
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Comuzzie
authors.forename: Michael C
authors.initials: MC
authors.lastname: Mahaney
authors.forename: Laura
authors.initials: L
authors.lastname: Almasy
authors.forename: Jean W
authors.initials: JW
authors.lastname: MacCluer
authors.forename: Ahmed H
authors.initials: AH
authors.lastname: Kissebah
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Collier
authors.forename: Eric K
authors.initials: EK
authors.lastname: Moses
authors.forename: John
authors.initials: J
authors.lastname: Blangero
mesh_terms: D000581:Amidohydrolases / Q000235:genetics; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics; D008076:Cholesterol, HDL / Q000235:genetics / Q000378:metabolism; D058851:GPI-Linked Proteins; D020869:Gene Expression Profiling; D008040:Genetic Linkage; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D017058:Mexican Americans / Q000235:genetics; D010641:Phenotype; D011401:Promoter Regions, Genetic; D040641:Quantitative Trait Loci; D014158:Transcription, Genetic
chemical_list: D015815:Cell Adhesion Molecules; D008076:Cholesterol, HDL; D058851:GPI-Linked Proteins; D005819:Genetic Markers; D000581:Amidohydrolases; C022314:pantetheinase