Overtime course of Harvey Bradshaw Index.

<p>The line represents the mean score and the error bars represent the standard error at each time point.</p

Effects of anti-TNF-α infusion on disease activity, fatigue, quality of life and mood compared to baseline reference value.

<p>HBI: Harvey-Bradshaw Index, CDAI: Crohn's Disease Activity Index, MFI: Multidimensional Fatigue Inventory, IBDQ: Inflammatory Bowel Disease Questionnaire, HDRS: Hamilton Depression Rating Scale, BDI: Beck Depression Inventory, SCL-90: Symptom Checklist.</p

Immune parameters and TRP/CAA at each time point.

<p>The results were presented as mean (<i>sd</i>).</p><p>TRP/CAA: tryptophan/competing aminoacids.</p

Association between SCL-90 depression scores and immune parameters and TRP/CAA over time.

a<p>without correction for disease activity ^bcorrected for disease activity</p><p>SCL-90: Symptom Checklist, TRP/CAA: tryptophan/competing aminoacids.</p

Effects of anti-TNF-α infusion on immune parameters and TRP/CAA compared to baseline reference value.

<p>TRP/CAA: tryptophan/competing aminoacids.</p

White noise speech illusion and the levels of schizotypy.

<p>White noise speech illusion and the levels of schizotypy.</p

Summary of selected demographic variables.

<p>Summary of selected demographic variables.</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