LSC Abstract – Association of single nucleotide polymorphisms located in miRNA binding sites with lung function

Abstract

Introduction: Genome-wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) that seem to be involved in human disease risk. However, only a few of these variants appear to have a causal role. MicroRNAs (miRNAs) regulate gene expression by binding to partially complementary sequences on target mRNA transcripts. SNPs that are located in these miRNA binding sites might alter miRNA regulation. Aims: The objective of our study was to identify SNPs in miRNA binding sites that are associated with lung function. Methods: Data on the association between SNPs in miRNA binding sites and FEV 1 , FEV 1 /FVC or FVC were obtained from the GWAS studies of Soler Artigas et al 1 and of Loth et al 2 . We examined the correlation of the miRNA binding site-SNPs with the expression of their host genes in blood using cis-eQTL data (n=8086). Results: 24.500 SNPs were located in the predicted binding site of miRNAs. The SNPs significantly associated with lung function parameters are listed in table 1. Table 1 Conclusions: In this study we identified multiple SNPs in miRNA binding sites that are associated with lung function and are likely to affect miRNA-mediated regulation. Interestingly, some of these SNPs also seem to have an effect on the expression of their host genes, suggesting a functional role. 1. Artigas M.S. et al. Nat Genet 2012; 43(11):1082-1090. 2. Loth D.W. et al. Nat Genet 2014;46(7):669-77. This abstract has been presented previously at the European Respiratory Society9s Lung Science Conference in March 2016.