SNPs that modify miRNA binding sites according to PolymiRTS Database.

<p>PolymiRTS Database uses the criteria of TargetScan for miRNA binding sites prediction.</p>(a)<p>Support column indicates occurrence of the miRNA site in other vertebrate genomes in addition to the query genome.</p>(b)<p>Function Class specifies if the derived allele either disrupts a non conserved miRNA site (N) or creates a new miRNA site (C).</p

Allele and genotype frequencies of <i>BDNF</i> polymorphism rs6265 (Val66Met) in control subjects and schizophrenic patients.

<p>Allele and genotype frequencies of <i>BDNF</i> polymorphism rs6265 (Val66Met) in control subjects and schizophrenic patients.</p

Luciferase assays for validation of miR-26a and -26b binding to <i>BDNF</i> 3′UTR.

<p>HeLa cells were independently transfected with control plasmid (pRL-TK) or each of the two reporter plasmid (pluc-BDNF C–G, anc, and pluc-BDNF A–T, der) with either miR-26a or miR-26b. Data are presented as the normalized activity of different reporter genes. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0028656#s1" target="_blank">Introduction</a> of exogenous miR-26a and miR-26b represses reporter activity of pluc-BDNF C–G but has no effect on pluc-BDNF A–T. Data represent the mean of five independent experiments +SD (<i>p</i><0.05).</p

Analysis output with miRecords, that integrates predicted miRNA targets produced by 11 miRNA target prediction programs.

<p>Here are reported programs that predict <i>BDNF</i> 3′UTR miRna binding sites for miRNAs identified with PolymiRTS. Other programs are: DIANA-microT, MicroInspector, MirTarget2, miTarget, NBmiRTar, PicTar, TargetScan and RNA22.</p

Schematic representation of base pairing between miR-26a sequence and <i>BDNF</i> 3′UTR ancestral (C–G) and derivative (A–T) alleles of rs11030100 and rs11030099 polymorphic sites.

<p>MiR-26b has the same seed binding sequence.</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