Ten years of enhancing neuro‐imaging genetics through meta‐analysis: An overview from the ENIGMA Genetics Working Group

• Published in: Human brain mapping Vol. 43; no. 1; pp. 292 - 299
• Main Authors: Medland, Sarah E., Grasby, Katrina L., Jahanshad, Neda, Painter, Jodie N., Colodro‐Conde, Lucía, Bralten, Janita, Hibar, Derrek P., Lind, Penelope A., Pizzagalli, Fabrizio, Thomopoulos, Sophia I., Stein, Jason L., Franke, Barbara, Martin, Nicholas G., Thompson, Paul M.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.01.2022
• Subjects: Alzheimer's disease; Brain; Brain - anatomy & histology; Brain - diagnostic imaging; Consortia; Genetic analysis; Genetic effects; Genetics; Genome-Wide Association Study; Genomes; GWAS; Heterogeneity; Humans; Magnetic resonance imaging; Medical imaging; Mental Disorders - diagnostic imaging; Mental Disorders - genetics; Mental Disorders - pathology; Meta-analysis; Meta-Analysis as Topic; Motivation; MRI; Multicenter Studies as Topic; Nervous System Diseases - diagnostic imaging; Nervous System Diseases - genetics; Nervous System Diseases - pathology; Neuroimaging; Neurological diseases; neuro‐imaging genetics; Quality control; Reproducibility; Review; Reviews; Sample size; MRI; neuro-imaging genetics; GWAS
• ISSN: 1065-9471; 1097-0193
• DOI: 10.1002/hbm.25311

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. Improvement in the polygenic score prediction of hippocampal volume, as power in the discovery GWAS increases. PRS may be thought of as weighted‐sum scores that summarize the results of the GWAS to a given level of significance, these results show the increased explanatory power of the GWAS for hipocampal volume as sample size increases.