MODULE STATUS

Developer contacts: ADHD: Maria Soler & Natalia Llonga

Developer contact: AD and Psoriasis: Josine Min

Scripts status: Ready

Prerequisite scripts: script 00, 01, 02, 03a-03d

Data upload method: Manual upload to GoogleDrive

PRS EWAS

A PRS EWAS will be performed on a range of complex traits, although you do not need any phenotypic data. If you have cord blood samples, you don't need to run this script.

Please run the following script to carry out the analyses:

./09-PRS_EWAS.sh

This script will loop through the different traits and for each trait it will:

• Generate the PRS using the weights provided in the parameters file.
• Standardise PRS to mean 0 and standard deviation of 1 and generate a histogram. When optional phenotype data are also provided additional plots will be generated to assess the relationship between the PRS and phenotypes provided as a positive control.
• For ADHD, run EWAS on untransformed methylation values adjusted for age, sex, cell counts, predicted smoking and genetic PCs, and relatedness for those studies with related individuals. A sensitivity analysis including also non-genetic methylation PCs will be implemented.
• For AD and psoriasis, run EWAS on untransformed methylation values adjusted for age, sex, cell counts, predicted smoking and genetic PCs, and relatedness for those studies with related individuals. A sensitivity analysis including also non-genetic methylation PCs will be implemented.

We are going to followup this analysis with reverse gear Mendelian randomization.

Please note that the logfile may show the following error message:

Error in chol.default(K) :
  the leading minor of order 3 is not positive definite

These errors are nothing to worry about. The function will simply omit these from the output and continue generating other outputs. We have decided to retain the error messages to indicate that statistics for some associations may be missing from the report as the model failed to converge for some of the CpGs.

Check, compress and upload the results to GoogleDrive

To check that everything has run successfully, please execute:

./check_upload.sh 09 check

To compress and encrypt the result files please run:

./check_upload.sh 09 upload

Note that here you will need to enter your encryption passphrase once for each of the traits analysed.

At this point two compressed files would have been generated for each trait (PRS_${trait}_${study_name}.tgz.gpg and PRS_${trait}_${study_name}.tgz.md5sum) and saved in the results folder 09.

Please follow the steps below to upload these files into GoogleDrive:

1. Download them to your local machine first.
2. Then, upload them following this link: https://drive.google.com/drive/folders/1O6IYpJyLV2pu7AEy5sBvHN5aXBzsHV1S?usp=sharing
3. After that, please notify us by emailing Maria Soler & Natalia Llonga with the encryption passphrase.

That is all! Thank you so much for completing the pipeline!