Discovery of expression QTLs using large-scale transcriptional profiling in human lymphocytes.
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.
Göring
Harald H H
HH
Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas 78245, USA. hgoring@sfbrgenetics.org
Curran
Joanne E
JE
Johnson
Matthew P
MP
Dyer
Thomas D
TD
Charlesworth
Jac
J
Cole
Shelley A
SA
Jowett
Jeremy B M
JB
Abraham
Lawrence J
LJ
Rainwater
David L
DL
Comuzzie
Anthony G
AG
Mahaney
Michael C
MC
Almasy
Laura
L
MacCluer
Jean W
JW
Kissebah
Ahmed H
AH
Collier
Gregory R
GR
Moses
Eric K
EK
Blangero
John
J
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
D015815:Cell Adhesion Molecules; D008076:Cholesterol, HDL; D058851:GPI-Linked Proteins; D005819:Genetic Markers; D000581:Amidohydrolases; C022314:pantetheinase