ENIGMA2: Genome-wide scans of subcortical brain volumes in 16,125 subjects from 28 cohorts. S. Medland, Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium Quantitative Genetics, Queensland Inst Med Res, Brisbane, Australia.

   The ENIGMA consortium (http://enigma.loni.ucla.edu) was founded in 2010 and brings together researchers in imaging genomics, to understand brain structure and function, based on MRI, DTI, fMRI and genome-wide association scan (GWAS) data. The consortium model is particularly important in neuroimaging, where the cost of phenotype collection almost three times the cost of genome-wide genotyping and contrary to the expectations of many, the distribution of effect sizes in neuroimaging genetics closely follows that seen in other complex traits such as height. The ENIGMA Consortium is comprised of 28 groups that span 5 continents, including 16,125 subjects. ENIGMA follows a meta-analysis framework, where analyses are conducted at local sites and group-level, de-identified statistics are contributed for meta-analysis. Image analysis is conducted using fully-automated and validated neuroimaging segmentation algorithms (FSL FIRST, FreeSurfer, or validated DTI processing pipelines). In the initial flagship project (Stein et al, 2012) we undertook GWAS meta-analysis of hippocampal volume, intracranial volume, and total brain volume. Here we report the findings of the second ENIGMA meta-analyses, which extended the initial project to examine genetic influences on the volumes of subcortical structures using data imputed to the 1,000 Genome Project references. In this second round of analysis, we have already identified numerous novel genome wide significant associations including two regions influencing amygdala volume (8p23.1 and 9q22.1), two regions influencing the putamen (14q22.3 and 18q21.2), and one region influencing the thalamus (20p12.1). In addition, we have replicated our earlier findings for hippocampal volume (located at 12q24.22 and 12q14.3). Of particular note is the chromosome 18 region influencing putamen located in DCC which is involved in axonal guidance of dopaminergic neurons and has previously been associated with schizophrenia. These findings have important implications for the identification and use of neuro-imaging endophenotypes for psychiatric and neurological disorders. The full list of contributing authors is available at http://enigma.loni.ucla.edu/ongoing/gwasma-of-subcortical-structures/ASHG2013/.

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