SMR-IVW is an extension of the SMR software that additionally allows to perform univariable and multivariable inverse-variance weighting (IVW) Mendelian randomization (MR) analyses on omics and GWAS summary data.
If you use this software please consider citing the original multi-SNP-based SMR method and software:
Wu Y, Zeng J, Zhang F, Zhu Z, Qi T, Zheng Z, Lloyd-Jones LR, Marioni RE, Martin NG, Montgomery GW, Deary IJ, Wray NR, Visscher PM, McRae AF & Yang J (2018) Integrative analysis of omics summary data reveals putative mechanisms underlying complex traits. Nature Communications, 9: 918
as well as the extension to univariable and multivariable MR-IVW analyses:
Sadler MC, Auwerx C, Porcu E & Kutalik Z (2022) Quantifying the role of transcript levels in mediating DNA methylation effects on complex traits and diseases. Nature Communications, 13:7759
The software works on Unix / Linux platforms (tested on CentOS Linux release 7.9.2009 (Core)). Download the latest release of the executable here (about 2MB < 1min download time).
Then unzip (if necessary), rename the software (optional) and change permissions if necessary as follows:
gzip -d smrivw_1.0.gz
mv smrivw_1.0 smrivw
chmod +rwx smrivwAlternatively compile the package making sure all the paths (e.g. Eigen library) point to the right location on your system.
Extensive documentation on data management functions (e.g. formatting input files, filtering input files) can be found on the official SMR website.
Documentation of univariable and multivariable MR-IVW is provided on this Github-Wiki.
As a starter run the examples inside the examples/ folder as follows (if necessary change the path of the executable):
bash run_examples.shThe expected output is shown in the examples/expected_output/ folder. The first example computes the univariable and multivariable MR effects of the DNA methylation probe cg07689907 on Triglycerides (TRI) via the transcript FADS2. The second examples computes the same MR causal effects but with the output being Apolipoprotein A (APOA). Details on the column headers and used formulas are found in the Multivariable MR (Mediation analysis) Wiki Page. The example data contains a subset of the 1000 Genomes (European ancestry) reference panel, DNA methylation QTL effects from the GoDMC consortium, eQTL effects from the eQTLGen consortium and GWAS effect sizes from the UK Biobank. Note that in order to reproduce results in the manuscript, it is recommended to use the UK10K reference panel which better matches allele frequencies of the other datasets. The expected run time should be less than 1 minute.
Pull requests are welcome. For major changes, please open an issue first to discuss what you would like to change.