RT Journal Article
SR Electronic
T1 meQTL analysis of asthma GWAS loci and DNA methylation
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP PA1209
DO 10.1183/13993003.congress-2016.PA1209
VO 48
IS suppl 60
A1 Ashish Kumar
A1 Cilla Söderhäll
A1 Simon Merid
A1 Chengjian Xu
A1 Olena Gruzieva
A1 Gerard Koppelman
A1 Juha Kere
A1 Göran Pershagen
A1 Erik Melén
YR 2016
UL http://erj.ersjournals.com/content/48/suppl_60/PA1209.abstract
AB Background: Asthma is characterized as a chronic inflammation disease and has increased in prevalence over the decades. Genome-wide association studies (GWAS) have implicated several single nucleotide polymorphisms (SNPs) with varying risk estimates for asthma, but the etiology is still not fully understood.Objective: To investigate the association between genetic and epigenetic (methylation) variations in six common GWAS asthma genes - ORMDL3, GSDMB, IL1RL1, IL4R, TSLP and WDR36, we explored the cis and trans-regulatory effects to identify SNPs associated with altered DNA methylation (meQTL) in 500kb buffer region and how top GWAS SNPs relate with resulting SNP-CpG hits.Methods: Using peripheral blood of 231 eight-year-old children with a doctor's diagnosis of asthma ever and 233 controls, from the BAMSE study, DNA methylation was measured on Illumina 450K beadchip and SNPs were assessed on Illumina610-Quad beadchip, imputed on 1000 Genomes reference panels. To identify meQTLs, CpG methylation values were regressed on SNP dosages with sex, asthma status and population stratification eigenvalues as covariates.Results: After applying genome-wide Bonferroni significance thresholds, we had significant SNP-CpG pair hits. The top hits for ORMDL3/GSDMB was cg26162295-rs8081462 (p=4.89x10-50) while LD with GWAS top SNP rs7216389 is r2=0.46. Similarly for IL1RL1, cg09003973-rs11902044 was top hit (p=5.76x10-32) and for TSLP, cg13681701-rs35188965 was top hit (p=4.47x10-71), with no LD to their top GWAS SNPs ( r2<0.05)Conclusion: Our results indicate that most CpG sites were associated with SNPs manifesting cis-effects. Thus, studying these meQTLs can help us disentangle some of the molecular mechanisms of asthma better.