Regions demonstrating differential functional connectivity with the left dorsolateral prefrontal cortex and left inferior parietal lobe seed regions during the 8s delay versus 0.5s implicit baseline condition for 21 young people exposed to severe childhood abuse and 27 healthy controls.

<p>P-value is <0.05 FWER corrected.</p

Performance measures for the sustained attention task during 2s, 5s and 8s delays for 21 abused young people and 27 healthy controls.

<p>MRT = mean reaction time (in ms); SDintrasubject = intrasubject variability of mean reaction times (in ms); corr = Bonferroni corrected; CA = childhood abuse; HC = healthy control.</p

Functional connectivity differences between 21 physically maltreated young people and 27 healthy controls for the 8s delay condition vs 0.5s baseline.

<p>Illustrating regions that demonstrated reduced connectivity for maltreated participants compared to healthy controls with A) the seed region of the left dorsolateral prefrontal cortex and B) the left inferior parietal seed region. The threshold is P < 0.05 FWE corrected at the cluster level. Z-coordinates represent distance from the anterior–posterior commissure in mm. The right side of the image corresponds to the right side of the brain.</p

Demographic characteristics of 21 young people exposed to severe childhood abuse and 27 healthy controls (CA = childhood abuse; HC = healthy controls; ADHD = attention deficit hyperactivity disorder; PTSD = post-traumatic stress disorder; ODD = oppositional defiant disorder; CD = conduct disorder).

<p>Demographic characteristics of 21 young people exposed to severe childhood abuse and 27 healthy controls (CA = childhood abuse; HC = healthy controls; ADHD = attention deficit hyperactivity disorder; PTSD = post-traumatic stress disorder; ODD = oppositional defiant disorder; CD = conduct disorder).</p

Significant GxE interaction effect between group (childhood abuse vs. healthy controls) and rs3800373 genotype (CC vs AC/AA) on functional connectivity between left IPL and DLPFC, p < 0.05.

<p>Significant GxE interaction effect between group (childhood abuse vs. healthy controls) and rs3800373 genotype (CC vs AC/AA) on functional connectivity between left IPL and DLPFC, p < 0.05.</p

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies