CAS_eQTL

This repository contains the scripts I used for the CAS (r)eQTL project.

Preprint: https://www.biorxiv.org/content/10.1101/683086v1

Peer reviewed article: https://www.nature.com/articles/s41467-020-17477-x

Huang, Q.Q., Tang, H.H.F., Teo, S.M., Ritchie, S.C., Nath, A.P. et al. Neonatal genetics of gene expression reveal the origins of autoimmune and allergic disease risk. Nat Commun 11, 3761 (2020)

eQTL mapping

1_Input_data_MatrixeQTL.R

Generate input files for Matrix eQTL.

2_Run_MatrixeQTL.R

Perform eQTL mapping using Matrix eQTL.

3_Run_eigenMT_using_all_CAS_genotype.R

Perform eigenMT to estimate the number of independent SNPs/tests in the 2-Mb window for each gene.

4_Multiple_testing_correction.R

Correct for multiple testing (local correction: eigenMT; global correction: BH FDR) and get the list of significant cis-eQTLs.

5_LD_top_eSNPs_two_conditions.R

For eGenes that were significant in both resting and stimulated cells (monocytes or T cells), calculate the LD correlation between the two top eSNPs from these two conditions. (This is actually for response eQTL mapping)

6_Conditional_analysis.R

Two stage conditional analysis.

7_Calculate_LD_eSNPs_topeSNP.R

For each significant eQTL SNP, calculate the LD correlation with the top eSNP of the corresponding gene.

Response eQTL mapping

1_Interaction_test_topeSNPs_permutation.R

Perform interaction tests on top eSNPs and run permutations.

2_Multiple_testing_correction.R

Apply BH-FDR on permutation adjusted P-values to correct for multiple testing and get significant reQTLs.

3_ReQTL_SuppleTable.R

Gather some more information on the reQTLs for supplemental table 7 and 8.

Trans-eQTL mapping and mediation analysis

1_Run_MatrixeQTL_genomewide.R

Perform genome-wide eQTL mapping using Matrix eQTL (output and write tests with P-value ≤1e-5).

2_MTC_genomewideFDR_geneFDR_geneBonf.R

Multiple testing using three ways: genome-wide FDR, gene-level FDR, gene-level Bonferroni.

3_Mediation_analysi_cis_trans.R

Get all mediation trios (eQTL–cis-eGene–trans-eGene) and perform mediation analysis.

4_Significant_Mediations.R

Apply BH FDR controlling procedure to correct for multiple testing.

5_LD_eSNPs_top_transeSNP_SNPinfo_SuppleTable.R

Calculate the LD correlation between each trans-eQTL SNP and the corresponding top SNP, and gather information for supplemental table 10.

Colocalisation analysis

1_Subset_GWAS_loci_candidate.R

Find loci where GWAS and eQTL signals have overlap, and prepare input data for coloc.

2_Perform_coloc_test.R

Perform colocalisation analysis using the R package coloc.

Mendelian randomisation analysis

0_1_MRbase_ciseQTLs_eGene_immunediseases.R

Get genetic instrumental variables and perform MR analysis using the R package TwoSampleMR.

0_2_MR_results_convert_list_to_dataframe.R

Extract MR test statistics.

1_MR_using_IVs_selected_by_TwoSampleMR.R

Perform the MR analysis again using Scott’s codes. The genetic IVs were harmonised and selected by the TwoSampleMR package.

2_Significant_MR_results_3_out_of_4_SuppleTable.R

Select significant causal associations and generate a supplementary table.

MR_functions_ScottRitchie_2019_04_17.R

I used this script from Scott Ritchie (https://github.com/sritchie73) to perform MR analysis and generate dose responsive curves.