Genome-wide identification of expression quantitative trait loci (eQTLs) in human heart.
In recent years genome-wide association studies (GWAS) have uncovered numerous chromosomal loci associated with various electrocardiographic traits and cardiac arrhythmia predisposition. A considerable fraction of these loci lie within inter-genic regions. The underlying trait-associated variants likely reside in regulatory regions and exert their effect by modulating gene expression. Hence, the key to unraveling the molecular mechanisms underlying these cardiac traits is to interrogate variants for association with differential transcript abundance by expression quantitative trait locus (eQTL) analysis. In this study we conducted an eQTL analysis of human heart. For a total of 129 left ventricular samples that were collected from non-diseased human donor hearts, genome-wide transcript abundance and genotyping was determined using microarrays. Each of the 18,402 transcripts and 897,683 SNP genotypes that remained after pre-processing and stringent quality control were tested for eQTL effects. We identified 771 eQTLs, regulating 429 unique transcripts. Overlaying these eQTLs with cardiac GWAS loci identified novel candidates for studies aimed at elucidating the functional and transcriptional impact of these loci. Thus, this work provides for the first time a comprehensive eQTL map of human heart: a powerful and unique resource that enables systems genetics approaches for the study of cardiac traits.
Department of Experimental Cardiology, Heart Failure Research Centre, Academic Medical Center, Amsterdam, The Netherlands.
Tamara T
TT
Koopmann
Department of Experimental Cardiology, Heart Failure Research Centre, Academic Medical Center, Amsterdam, The Netherlands.
Michiel E
ME
Adriaens
Bioinformatics Laboratory, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherlands.
Perry D
PD
Moerland
Department of Experimental Cardiology, Heart Failure Research Centre, Academic Medical Center, Amsterdam, The Netherlands.
Roos F
RF
Marsman
Department of Experimental Cardiology, Heart Failure Research Centre, Academic Medical Center, Amsterdam, The Netherlands.
Margriet L
ML
Westerveld
Muscle Research Unit, Department of Anatomy, Bosch Institute, The University of Sydney, Sydney, Australia.
Sean
S
Lal
Department of Medicine, University of Miami School of Medicine, Miami, Florida, United States of America.
Taifang
T
Zhang
Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee, United States of America.
Christine Q
CQ
Simmons
Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary.
Istvan
I
Baczko
Muscle Research Unit, Department of Anatomy, Bosch Institute, The University of Sydney, Sydney, Australia.
Cristobal
C
dos Remedios
Department of Medicine, University of Miami School of Medicine, Miami, Florida, United States of America; Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, Florida, United States of America.
Nanette H
NH
Bishopric
Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary.
Andras
A
Varro
Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee, United States of America.
Alfred L
AL
George
Department of Experimental Cardiology, Heart Failure Research Centre, Academic Medical Center, Amsterdam, The Netherlands.
Elisabeth M
EM
Lodder
Department of Experimental Cardiology, Heart Failure Research Centre, Academic Medical Center, Amsterdam, The Netherlands.
Connie R
CR
Bezzina
D001145:Arrhythmias, Cardiac / Q000235:genetics* / Q000378:metabolism; D002877:Chromosomes, Human / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci