“Ten Years of Enhancing Neuro-Imaging Genetics through Meta-Analysis: An Overview from the ENIGMA Genetics Working Group”, 2020-12-10 (; similar):
Here we review the motivation for creating the enhancing neuroimaging genetics through meta-analysis (ENIGMA) Consortium and the genetic analyses undertaken by the consortium so far. We discuss the methodological challenges, findings, and future directions of the genetics working group. A major goal of the working group is tackling the reproducibility crisis affecting “candidate gene” and genome-wide association analyses in neuroimaging. To address this, we developed harmonized analytic methods, and support their use in coordinated analyses across sites worldwide, which also makes it possible to understand heterogeneity in results across sites. These efforts have resulted in the identification of hundreds of common genomic loci robustly associated with brain structure. We have found both pleiotropic and specific genetic effects associated with brain structures, as well as genetic correlations with psychiatric and neurological diseases.
Why Did We Build The Enigma Consortium? The consortium was formed in 2009, largely in response to the growing evidence of a lack of reproducibility dubbed “the replication crisis” in imaging genetics. At this time, the first major works of the Psychiatric Genomics Consortium were being presented at conferences ( et al 2010; The Schizophrenia Psychiatric Genome-Wide Association Study [GWAS] Consortium, 2011a, 2011b), and we had observed the improvement in statistical power and increase in reproducibility that could be achieved through large-scale meta-analysis. In late 2009, we were beginning to see a series of GWAS publications using phenotypes derived from magnetic resonance imaging (MRI) attempting to answer complex and important questions in psychiatry and neurology. At that time, it was common to see GWAS papers reporting not only main effect analyses but also interactions with diagnosis or putative risk variables in sample sizes of less than 1,000 people.
…In response to these issues, Thompson and Martin sent an email to neuro-imaging groups around the world asking for interest in being part of a collaborative meta-analysis consortium focusing on imaging genetics. The key points in this email were that, although every group would understandably want to publish its own paper reporting their own findings, (a) the power calculations do not change just because the phenotype acquisition is expensive, (b) it was likely that the individual studies would not be large enough to find statistically-significant genetic effects, and (c) even if they did, it would still be necessary to replicate these findings in independent samples. From these beginnings, the ENIGMA consortium now involves more than 2,000 scientists from over 400 institutions in more than 40 countries.