Integrated genome-wide analysis of expression quantitative trait loci aids interpretation of genomic association studies

Background Identification of single nucleotide polymorphisms (SNPs) associated with gene expression levels, known as expression quantitative trait loci (eQTLs), may improve understanding of the functional role of phenotype-associated SNPs in genome-wide association studies (GWAS). The small sample s...

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Vydáno v:	Genome Biology Ročník 18; číslo 1; s. 16
Hlavní autoři:	Joehanes, Roby, Zhang, Xiaoling, Huan, Tianxiao, Yao, Chen, Ying, Sai-xia, Nguyen, Quang Tri, Demirkale, Cumhur Yusuf, Feolo, Michael L., Sharopova, Nataliya R., Sturcke, Anne, Schäffer, Alejandro A., Heard-Costa, Nancy, Chen, Han, Liu, Po-ching, Wang, Richard, Woodhouse, Kimberly A., Tanriverdi, Kahraman, Freedman, Jane E., Raghavachari, Nalini, Dupuis, Josée, Johnson, Andrew D., O’Donnell, Christopher J., Levy, Daniel, Munson, Peter J.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London BioMed Central 25.01.2017 Springer Nature B.V
Témata:	Adult Aged Alleles Animal Genetics and Genomics as Revealed Through Genomics Bioinformatics Biomedical and Life Sciences Blood Cluster Analysis Coronary artery coronary artery disease Disease DNA methylation DNA microarrays Evolutionary Biology exons Female Gene Expression Gene Expression Profiling Gene Frequency Genetic Predisposition to Disease genome-wide association study Genome-Wide Association Study - methods Genomes Genomics Genomics - methods Heart diseases Human Genetics human physiology Humans Life Sciences loci Male meta-analysis microarray technology Microbial Genetics and Genomics microRNA MicroRNAs - genetics Middle Aged miRNA pathophysiology phenotype Phenotypes Plant Genetics and Genomics Polymorphism Polymorphism, Single Nucleotide Quantitative Trait Loci Regulatory Sequences, Nucleic Acid Reproducibility of Results Single-nucleotide polymorphism Studies The Biology of Human Diseases Web Browser Framingham Heart Study Transcript Cluster eQTL Study Cluster Pair Exon Array
ISSN:	1474-760X, 1474-7596, 1474-760X
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Popis
Shrnutí:	Background Identification of single nucleotide polymorphisms (SNPs) associated with gene expression levels, known as expression quantitative trait loci (eQTLs), may improve understanding of the functional role of phenotype-associated SNPs in genome-wide association studies (GWAS). The small sample sizes of some previous eQTL studies have limited their statistical power. We conducted an eQTL investigation of microarray-based gene and exon expression levels in whole blood in a cohort of 5257 individuals, exceeding the single cohort size of previous studies by more than a factor of 2. Results We detected over 19,000 independent lead cis -eQTLs and over 6000 independent lead trans -eQTLs, targeting over 10,000 gene targets (eGenes), with a false discovery rate (FDR) < 5%. Of previously published significant GWAS SNPs, 48% are identified to be significant eQTLs in our study. Some trans -eQTLs point toward novel mechanistic explanations for the association of the SNP with the GWAS-related phenotype. We also identify 59 distinct blocks or clusters of trans -eQTLs, each targeting the expression of sets of six to 229 distinct trans -eGenes. Ten of these sets of target genes are significantly enriched for microRNA targets (FDR < 5%). Many of these clusters are associated in GWAS with multiple phenotypes. Conclusions These findings provide insights into the molecular regulatory patterns involved in human physiology and pathophysiology. We illustrate the value of our eQTL database in the context of a recent GWAS meta-analysis of coronary artery disease and provide a list of targeted eGenes for 21 of 58 GWAS loci.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1474-760X 1474-7596 1474-760X
DOI:	10.1186/s13059-016-1142-6