title: Identification of common genetic variants controlling transcript isoform variation in human whole blood.
abstract: An understanding of the genetic variation underlying transcript splicing is essential to dissect the molecular mechanisms of common disease. The available evidence from splicing quantitative trait locus (sQTL) studies has been limited to small samples. We performed genome-wide screening to identify SNPs that might control mRNA splicing in whole blood collected from 5,257 Framingham Heart Study participants. We identified 572,333 cis sQTLs involving 2,650 unique genes. Many sQTL-associated genes (40%) undergo alternative splicing. Using the National Human Genome Research Institute (NHGRI) genome-wide association study (GWAS) catalog, we determined that 528 unique sQTLs were significantly enriched for 8,845 SNPs associated with traits in previous GWAS. In particular, we found 395 (4.5%) GWAS SNPs with evidence of cis sQTLs but not gene-level cis expression quantitative trait loci (eQTLs), suggesting that sQTL analysis could provide additional insights into the functional mechanism underlying GWAS results. Our findings provide an informative sQTL resource for further characterizing the potential functional roles of SNPs that control transcript isoforms relevant to common diseases.
authors: 1] Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA. [2] National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.
authors: Xiaoling
authors: X
authors: Zhang
authors: 1] Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA. [2] National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA. [3] Mathematical and Statistical Computing Laboratory, Center for Information Technology, US National Institutes of Health, Bethesda, Maryland, USA.
authors: Roby
authors: R
authors: Joehanes
authors: 1] Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA. [2] National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.
authors: Brian H
authors: 0000000190653301
authors: BH
authors: Chen
authors: 1] Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA. [2] National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.
authors: Tianxiao
authors: T
authors: Huan
authors: Mathematical and Statistical Computing Laboratory, Center for Information Technology, US National Institutes of Health, Bethesda, Maryland, USA.
authors: Saixia
authors: S
authors: Ying
authors: Mathematical and Statistical Computing Laboratory, Center for Information Technology, US National Institutes of Health, Bethesda, Maryland, USA.
authors: Peter J
authors: PJ
authors: Munson
authors: 1] Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA. [2] National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.
authors: Andrew D
authors: AD
authors: Johnson
authors: 1] Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA. [2] National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.
authors: Daniel
authors: D
authors: Levy
authors: 1] Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA. [2] National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA. [3] Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Christopher J
authors: CJ
authors: O'Donnell
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D001483:Base Sequence; D001773:Blood Cells / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004194:Disease / Q000235:genetics; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D020033:Protein Isoforms / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics*; D022821:RNA Splice Sites / Q000235:genetics; D059467:Transcriptome
chemical_list: D020033:Protein Isoforms; D022821:RNA Splice Sites