B611 - Validation and Replication of Genetic Variants in Predicted microRNA Binding Sites and their Effect on mRNA Expression Levels - 31/01/2008

B number: 
B611
Principal applicant name: 
Dr Cecilia Lindgren (University of Oxford, UK)
Co-applicants: 
Nick Timpson (University of Bristol, UK), Mahim Jain (University of Oxford, UK)
Title of project: 
Validation and Replication of Genetic Variants in Predicted microRNA Binding Sites and their Effect on mRNA Expression Levels
Proposal summary: 

Scientific case for doing the genetic association study in ALSPAC (up to about three pages) :

Genetic variation is associated with mRNA expression levels in a heritable fashion and has been mapped in humans and model organisms as expression quantitative trait loci (eQTL). We have previously determined a number of associations between genetic variation in microRNA (miRNA) binding-sites and target mRNA expression levels.We have identified 18 genetic variants in miRNA binding-sites that are significantly associated with target gene expression levels after stringent permutations in the HapMap CEU samples and that replicate in other populations and on multiple platforms. For five miRNA binding-site variants, we are able to narrow the interval of association of which two are the most associated variants in the region. This is consistent with the hypothesis that this is the true regulatory variant. Furthermore, we find an over-representation of significant miRNA binding SNPs associated with target mRNA expression levels compared to most other annotation classes.

Given the initial evidence that SNPs within microRNA binding sites effect mRNA expression levels, we hope to further replicate these findings in other samples. The ALSPAC dataset serves as an excellence and unique resource for this endeavour.

Date proposal received: 
Thursday, 31 January, 2008
Date proposal approved: 
Thursday, 31 January, 2008
Keywords: 
Genetics
Primary keyword: