Open AccessIdentification of common genetic variants controlling transcript isoform variation in human whole blood
Author(s) -
Xiaoling Zhang,
Roby Joehanes,
Brian H. Chen,
Tianxiao Huan,
Saixia Ying,
Peter J. Munson,
Andrew D. Johnson,
Daniel Levy,
Christopher J. O’Donnell
Publication year - 2015
Publication title -
nature genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 18.861
H-Index - 573
eISSN - 1546-1718
pISSN - 1061-4036
DOI - 10.1038/ng.3220
Subject(s) - biology , genome wide association study , quantitative trait locus , single nucleotide polymorphism , expression quantitative trait loci , genetics , alternative splicing , genetic association , gene , locus (genetics) , framingham heart study , rna splicing , human genome , genome , computational biology , gene isoform , disease , genotype , framingham risk score , rna , medicine , pathology
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.