Imaging Genetics: From Neanderthals To Modern Human's Psychiatric Disorders

Abstract

Overall Abstract The structure of our brain is intricately linked to its functioning and malfunctioning. Indeed, alterations in brain structure are observed in all psychiatric disorders, but such findings are still often based on suboptimal sample sizes. Within the ENIGMA consortium, we bring together scientists from all parts of the world interested in imaging and imaging genetics. This has allowed us to integrate data on MRI-assessed brain gray and white matter across health and disease reaching unprecedented sample sizes. Pooling of data from multiple cohorts provides more accurate effect size estimates on brain structure alteration in psychiatric disorders, contributes new information on trajectories of disease-related brain volume alterations across the lifespan, and clarifies commonalities and differences between different psychiatric disorders. It is often not clear, whether observed brain structure alterations are a consequence of living with the disorder or are more likely linked to disease-causal processes. Genetics research may shed light on this. The imaging genetics community in ENIGMA has identified novel genetic variants linked to subcortical brain volumes and intracranial volume (ICV) in the largest sample sizes available, currently involving more than 35,000 participants (recent publications: Hibar et al., Nature 2015; Adams et al., Nature Neuroscience 2016; Hibar et al., Nature Communications 2017). During the symposium, we will also present new results from the study of global and regional measures of cortical thickness and surface area. Combining ENIGMA data with those from large consortia on the genetics of psychiatric disorders, the Psychiatric Genomics Consortium (PGC) and iPSYCH, we can identify potential etiologic links between brain structure and disease risk based on molecular genetic overlap. Surprisingly, a first study involving data on over 88,000 individuals did not provide evidence for overlap between schizophrenia risk variants and those for subcortical brain volume or ICV (Franke et al., Nature Neuroscience 2016). However, new data on ADHD, to be presented in the symposium, do show significant genetic overlap. Evolutionary aspects of brain performance and the involvement of genetics in this represent a research area of growing interest. Are psychiatric disorders the price we pay for the evolutionary recent expansion of our brain? This symposium will shed some light on the role of genetic loci linked to brain morphology changes from Neanderthals to modern humans and/or those having undergone accelerated evolution in hominids in influencing brain functioning and disease.