This repository contains the simulation and analysis scripts for the paper "Reconsidering the validity of transcriptome-wide association studies" (preprint). Content by directory is as follows:

main: scripts for real data analysis

• run_bivar.r: runs LAVA-rG and LAVA-TWAS
• run_fusion.bs: runs FUSION

lava: scripts for parts of LAVA analysis external to LAVA R package

• lava_twas.r: LAVA-TWAS code
• lava_approx.r: normal approximation for LAVA-rG bivariate analysis

simulations: scripts for generation and analysis of simulated data

• generate.r: generates input for all the analysis (both raw E and Y, and corresponding SNP summary statistics)
  • there are 10 different data blocks (from chromosomes 1-10), results are aggregated over thes blocks
  • each call generates 100 iterations for the specified phenotype sample size and number of SNPs
  • simulated values are generated for the full range of (relevant) heritability and expression sample size values
• run_comm.r: run CoMM analysis for a specific pair of conditions at a time
  • uses raw E and Y
• run_lava.r: run LAVA-TWAS analysis for all pairs of the list of input conditions (for specific number of SNPs in the block)
  • all analyses use the N=1000 genotype block as reference data, regardless of the sample sizes used when generating the data
  • uses summary statistics for both E and Y
• fusion_weights.bs: fits prediction models (BLUP, BSLMM, Elastic Net, LASSO) on the simulated expression
  • to make simulations computationally more feasible, cross-validation is turned off, and true r2 values used in the simulation process are provided to FUSION
  • uses raw E
• fusion_analysis.bs: runs TWAS analysis with fitted prediction models, for all combinations of expression and outcome conditions for given outcome sample size
  • all analyses use the N=1000 genotype block as reference data, regardless of the sample sizes used when generating the data
  • uses summary statistics for Y
• fusion (directory): contains three R helper scripts used in fusion_weights.bs and fusion_analysis.bs

figure data.zip additional archive with scripts and input data to generate the main text figures