Re-annotation of presumed noncoding disease/trait-associated genetic variants by integrative analyses

• DOI: 10.1038/srep09453
• Publication Date: 2015-03-30T09:14:35Z
• Authors: Geng Chen; Dianke Yu; Jiwei Chen; Ruifang Cao; Juan Yang; Huan Wang; Xiangjun Ji; Baitang Ning; Tieliu Shi
• Keywords: RefSeq; Genome-wide Association Study; Ensembl; Genetic Association; Nonsynonymous substitution

Abstract Using RefSeq annotations, most disease/trait-associated genetic variants identified by genome-wide association studies (GWAS) appear to be located within intronic or intergenic regions, which makes it difficult interpret their functions. We reassessed GWAS-Associated single-nucleotide polymorphisms (herein termed as GASs) for potential functionalities using integrative approaches. 8834 of 9184 “noncoding” GASs were have regulatory functionalities. As examples, 3 (rs3130320, rs3806932 and rs6890853) shown properties in HepG2, A549 293T cells. Except rs3130320 a known expression quantitative trait loci (eQTL), rs6890853 not reported eQTLs previous reports. 1999 re-annotated the promoters intragenic regions Ensembl, UCSC AceView gene annotations but they annotated into corresponding database. Moreover, these GAS-harboring genes broadly expressed across different tissues portion them was tissue-specific manner, suggesting that could functional. Collectively, our study demonstrates benefits analyses may help predict explain disease susceptibility more accurately comprehensively.