Heart Failure eQTLs companion to "Pathologic gene network rewiring implicates PPP1R3A as a central cardioprotective factor in pressure overload heart failure"

These are the results of a QTL analysis companion to "Pathologic gene network rewiring implicates PPP1R3A as a central cardioprotective factor in pressure overload heart failure". We performed RNA expression measurements and obtained genotype information in genome-wide markers for 313 patients (177 failing hearts , 136 donor, non-failing [control] hearts) using Affymetrix expression and Affymetrix Human 6.0 respectively.<strong> </strong>Prior to eQTL discovery, we used PEER to find hidden covariates that could confound signals in our data as well as filtering any genotypes with major allele frequencies less than 5%. To test associations between gene expression in each cohort separately, we used QTLTools with an additive model accounting for gender, age, sample site, and the PEER factors as covariates. We corrected for eQTL multiple association testing using a 10000 permutations per locus in a 2 megabase window and a false discovery rate cutoff of 5%. To select the number of PEER factors, we performed the full analysis multiple times from 1 to 15 PEER factors and observed a saturation of new QTLs being discovered when using 10 factors. Four files are provided, two for each cohort (cases and controls): - peer_[cases|controls]_nominal.txt: Nominal associations with a p-value threshold of 0.001 - peer_[cases|controls]_permutations_all.significant.txt: All significant associations detected after the QTLtools permutation test. The column names are those from QTLtools, in order: <br> 1. The phenotype ID<br> 2. The chromosome ID of the phenotype<br> 3. The start position of the phenotype<br> 4. The end position of the phenotype<br> 5. The strand orientation of the phenotype<br> 6. The total number of variants tested in cis<br> 7. The distance between the phenotype and the tested variant (accounting for strand orientation)<br> 8. The ID of the tested variant ( in Affy 6.0 SNP ids)<br> 9. The chromosome ID of the variant<br> 10. The start position of the variant<br> 11. The end position of the variant<br> 12. The nominal P-value of association between the variant and the phenotype<br> 13. The corresponding regression slope<br> 14. A binary flag equal to 1 is the variant is the top variant in cis