Analysis of genetically driven alternative splicing identifies FBXO38 as a novel COPD susceptibility gene.

Autor: Aabida Saferali, Jeong H Yun, Margaret M Parker, Phuwanat Sakornsakolpat, Robert P Chase, Andrew Lamb, Brian D Hobbs, Marike H Boezen, Xiangpeng Dai, Kim de Jong, Terri H Beaty, Wenyi Wei, Xiaobo Zhou, Edwin K Silverman, Michael H Cho, Peter J Castaldi, Craig P Hersh, COPDGene Investigators, International COPD Genetics Consortium Investigators
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: PLoS Genetics, Vol 15, Iss 7, p e1008229 (2019)
Druh dokumentu: article
ISSN: 1553-7390
1553-7404
DOI: 10.1371/journal.pgen.1008229
Popis: While many disease-associated single nucleotide polymorphisms (SNPs) are associated with gene expression (expression quantitative trait loci, eQTLs), a large proportion of complex disease genome-wide association study (GWAS) variants are of unknown function. Some of these SNPs may contribute to disease by regulating gene splicing. Here, we investigate whether SNPs that are associated with alternative splicing (splice QTL or sQTL) can identify novel functions for existing GWAS variants or suggest new associated variants in chronic obstructive pulmonary disease (COPD). RNA sequencing was performed on whole blood from 376 subjects from the COPDGene Study. Using linear models, we identified 561,060 unique sQTL SNPs associated with 30,333 splice sites corresponding to 6,419 unique genes. Similarly, 708,928 unique eQTL SNPs involving 15,913 genes were detected at 10% FDR. While there is overlap between sQTLs and eQTLs, 55.3% of sQTLs are not eQTLs. Co-localization analysis revealed that 7 out of 21 loci associated with COPD (p
Databáze: Directory of Open Access Journals
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