OA Epidemiology

A Bioinformatics Based in silico Post GWAS Analysis of CRP Variants

Proceedings of the 2013 annual meeting of the Netherlands Epidemiology Society

Volume 1 Issue S1 Abstract 54

 

A. Vaez, University Medical Center Groningen, The Netherlands
B. Prins, University Medical Center Groningen, The Netherlands
H.J. Westra, University Medical Center Groningen, The Netherlands
L. Franke, University Medical Center Groningen, The Netherlands
I. Nolte, University Medical Center Groningen, The Netherlands
H. Snieder, University Medical Center Groningen, The Netherlands
B.Z. Alizadeh, University Medical Center Groningen, The Netherlands

Background
Genome-wide association studies (GWAS) have been successful in finding Single Nucleotide Polymorphisms (SNPs) associated with complex traits. A recent meta-analysis of 25 GWAS studies has identified 18 SNPs associated with C-Reactive Protein (CRP) level. Nevertheless, a proper post-GWAS analysis for CRP variants is yet to be done. To translate CRP GWAS findings to biological function, here we present a sequential pipeline of bioinformatics based approaches to determine the functional characteristics of the 18 CRP-associated variants.

Methods
We firstly aimed to apply an ‘in silico’ sequencing analysis using 1000 Genomes Project data to identify nearby coding variants. Secondly, we aimed to perform an expression quantitative trait loci (eQTL) analysis using a large data set of blood expression probes to find regulatory variants. Thirdly, we aimed to integrate the findings of the abovementioned phases with original meta-GWAS results by performing a functional network analysis to find significantly enriched pathways.

Results
We found 3,801 SNPs which are linked to the 18 CRP-associated variants (r2>0.1), of which, 25 SNPs are non-synonymous SNPs. We also found 15 expression probes significantly associated with GWAS SNPs; these probes mainly map to other genes than the gene closest to the lead GWAS SNP. Our network  analysis on the molecular complexes within the first degree interaction network identified several regulatory pathways of CRP.

Conclusions
Our extended post-GWAS analyses of CRP variants has prioritized genes for functional follow up studies that may further elucidate the complex mechanisms by which genetic variation is ultimately translated into variability in CRP levels.

Published: 06 Jun, 2013

 
Licensee OA Publishing London 2013. Creative Commons Attribution License (CC-BY)