All ENIGMA protocols are now linked on the ENIGMA GitHub page page. Please check here for the latest amendments and updates!

ENIGMA Protocols for Imputation and Genetic Associations

Anyone is welcome to use these protocols for their projects! If you use the protocols on this site for projects outside of ENIGMA, please include a reference to the ENIGMA main page (http://enigma.usc.edu/) so that your readers and reviewers know about it as well. If you are using the 'ENIGMA1' protocols, please cite Stein et al., Nature Genetics, 2012. If you are using the 'ENIGMA2' protocols, please cite Hibar et al., Nature, 2015. If you are using the 'ENIGMA3' protocols, please cite Grasby et al., Nature, 2020.

Current Imputation Protocol

Below is the current imputation protocol for GWAS meta-analysis of Cortical and Subcortical ROIs.

Imputation Protocol (PDF) -- Updated (July 13 2017)

ENIGMA - GWAS Meta Analysis of DTI Metrics

Below are the protocols for GWAS meta-analysis of Diffusion Tensor Imaging (DTI) metrics.

IMPORTANT NOTE: Please make sure to preprocess and run your diffusion MRI data through the ENIGMA TBSS pipeline first and only use data for the subsequent preImputationQC from individuals who passed this pipeline.

Pre-Imputation Quality Control (QC) Protocol -- Updated: April 16, 2024: Now available on ENIGMA-Git - click here!The protocol can also be downloaded in HTML format: ENIGMA DTI GWAS Pre Imputation QC Protocol

This protocol explains first different scenarios related to different levels of previous genotype processing (i.e. for example, if you have contributed to previous ENIGMA GWAS versus if you have not previously processed (all) the genotype data). Please note: This PreImputationQC Protocol is meant to be run after you have completed the ENIGMA DTI phenotype extraction and QC protocols found on our GitHub.

Imputation Protocol: Under Construction

ENIGMA3 - GWAS Meta Analysis of Cortical Thickness and Surface Area

Below are the imputation and association protocols for GWAS meta-analysis of Cortical ROIs, aka the ENIGMA3 project. Note: For ENIGMA3 we will be using the same imputation protocol as used for the ENIGMA2 project.

- Same Protocol as ENIGMA2: Imputation Protocol (PDF) -- Updated (July 27, 2012)
- ENIGMA3 Association Protocols: Now available on ENIGMA-Git - click here!

The protocol can also be downloaded in Word format: ENIGMA3 Protocol

ENIGMA2 - GWAS Meta Analysis of Subcortical Volumes

Below are the imputation and association protocols for GWAS meta-analysis of subcortical volumes, aka the ENIGMA2 project.

{Legacy Version} ENIGMA1 - GWAS Meta Analysis of Hippocampal, Intracranial and Total Brain Volume

Below are the protocols from the ENIGMA pilot project (Stein et al., 2012, Nature Genetics):

Imputation to HapMap III
Association Protocol
Meta-Analysis Protocol (coming soon!)
Until the meta-analysis protocol is posted, an example protocol for meta-analysis used in an international GWAS consortium can be found here. We gratefully thank Margie Wright, Beben, and Peter from Queensland Institute for Medical Research, Australia.

ENIGMA-Epigenetics - EWAS Meta Analysis of blood DNA methylation

Below are the DNA Methylation quality control and epigenome-wide association studies protocols from the ENIGMA-Epigenetics Working Group.

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