The study population.

<p>The study population.</p

Regression lines for serum antidepressant concentrations across pregnancy.

<p>The figure shows the expected serum concentrations across pregnancy for women using the antidepressant doses presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0181082#pone.0181082.t002" target="_blank">Table 2</a>. The regression lines are shown in blue, and the 95% confidence limits with dashed black lines. For fluoxetine and venlafaxine the concentrations shown represent the active moiety (i.e. parent drug plus metabolite).</p

The serum antidepressant concentrations across pregnancy.

<p>The figure shows each of the observed serum concentrations in the study, adjusted to the doses presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0181082#pone.0181082.t002" target="_blank">Table 2</a>. Observations from the same women in non-pregnant state (baseline values) are shown as pregnancy week 0. Delivery is set to pregnancy week 40. Thus, for a woman who gave birth in week 38, a sample drawn x weeks after delivery would be shown x weeks to the right of the vertical delivery line. For fluoxetine and venlafaxine the concentrations shown represent the active moiety (parent drug + metabolite). Three outliers for escitalopram are not shown in the figure. These are one analysis in week 0 (concentration 36 ng/mL), one analysis in week 4 (concentration 36 ng/mL) and one analysis in week 5 (concentration 40 ng/mL). However, these concentrations are included in the statistical analyses. The horizontal lines represent the median (dark grey), 25 and 75 percentiles (light grey) and 10 and 90 percentiles (white) for dose-adjusted serum concentration measurements for all women aged 18–45 years from the St. Olav University Hospital TDM database. For further details, see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0181082#sec006" target="_blank">Methods</a> section.</p

Serum metabolite concentrations and parent compound/metabolite ratios at baseline and in the third trimester.

<p>Serum metabolite concentrations and parent compound/metabolite ratios at baseline and in the third trimester.</p

Serum antidepressant concentrations across pregnancy.

<p>Serum antidepressant concentrations across pregnancy.</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