Genetic variants inHHIPare associated with FEV1in subjects with chronic obstructive pulmonary disease

Respirology ◽  
2013 ◽  
Vol 18 (8) ◽  
pp. 1202-1209 ◽  
Author(s):  
Woo Jin Kim ◽  
Yeon-Mok Oh ◽  
Jin Hwa Lee ◽  
Choon-Sik Park ◽  
Sung Woo Park ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Genetic Variants ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease

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

2019 ◽  
Author(s):  
Aabida Saferali ◽  
Jeong H. Yun ◽  
Margaret M. Parker ◽  
Phuwanat Sakornsakolpat ◽  
Robert P. Chase ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Alternative Splicing ◽  
Pulmonary Disease ◽  
Lung Tissue ◽  
Genetic Variants ◽  
Unknown Function ◽  
Rna Splicing ◽  
Chronic Obstructive ◽  
Splice Sites ◽  
Obstructive Pulmonary Disease

AbstractWhile 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, 60% of sQTLs are not eQTLs. Co-localization analysis revealed that 7 out of 21 loci associated with COPD (p<1×10−6) in a published GWAS have at least one shared causal variant between the GWAS and sQTL studies. Among the genes identified to have splice sites associated with top GWAS SNPs was FBXO38, in which a novel exon was discovered to be protective against COPD. Importantly, the sQTL in this locus was validated by qPCR in both blood and lung tissue, demonstrating that splice variants relevant to lung tissue can be identified in blood. Other identified genes included CDK11A and SULT1A2.Overall, these data indicate that analysis of alternative splicing can provide novel insights into disease mechanisms. In particular, we demonstrated that SNPs in a known COPD GWAS locus on chromosome 5q32 influence alternative splicing in the gene FBXO38.Author SummaryWhile it is known that chronic obstructive pulmonary disease (COPD) is caused in part by genetic factors, few studies have identified specific causative genes. Genetic variants that alter the expression levels of genes have explained part of the genetic component of COPD, however, there are additional genetic variants with unknown function. In some genes the protein coding sequence can be altered by a mechanism known as RNA splicing. We hypothesized that some genetic variants that are associated with risk of COPD contribute to the disease by altering RNA splicing. In this study, we identified genetic variants that are associated both with COPD risk and RNA splicing. In particular, we found that a COPD associated variant of previously unknown function may contribute to the inclusion of a new exon in the FBXO38 gene. These finding are significant because they indicate that analysis of RNA splicing can help identify genes that contribute to disease.

scholarly journals Genetic Variants Associated with the Risk of Chronic Obstructive Pulmonary Disease with and without Lung Cancer

2011 ◽  
Vol 5 (3) ◽  
pp. 365-373 ◽  
Author(s):  
Mariza de Andrade ◽  
Yan Li ◽  
Randolph S. Marks ◽  
Claude Deschamps ◽  
Paul D. Scanlon ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Genetic Variants ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease

scholarly journals Common Genetic Variants Associated with Resting Oxygenation in Chronic Obstructive Pulmonary Disease

2014 ◽  
Vol 51 (5) ◽  
pp. 678-687 ◽  
Author(s):  
Merry-Lynn N. McDonald ◽  
Michael H. Cho ◽  
Inga-Cecilie Sørheim ◽  
Sharon M. Lutz ◽  
Peter J. Castaldi ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Genetic Variants ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Common Genetic Variants
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