7 research outputs found

    Protein-protein interaction network build from proteins encoded in associated intervals.

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    <p>The colored, full circles represent proteins encoded in associated intervals (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0122501#pone.0122501.s002" target="_blank">S2 Table</a>). The smaller, grey circles represent interactors of indirect connections. Functionally, the DAPPLE-constructed diagram can be divided into two main groups: group “A” mostly involved in the regulation of gene expression and inflammation; and group “B” mostly involved in cell adhesion.</p

    List of SNPs with observed association p-value being less than 1.00E-05.

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    <p>Chromosomal position is specified in Build 36 (hg18). OR refers to odds ratio and 95%CI refers to 95% confidence interval. <i>TRIM36</i> refers to tripartite motif containing 36 gene. <i>ZBTB16</i> refers to zinc finger and BTB domain containing 16 gene.</p><p>List of SNPs with observed association p-value being less than 1.00E-05.</p

    Results of protein-protein link evaluation in DAPPLE. List of indirect interactors.

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    <p>Presented p-values reflect the probability that by chance individual interactors would be as connected to seed proteins (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0122501#pone.0122501.s002" target="_blank">S2 Table</a>) as was observed in the constructed network.</p><p>Results of protein-protein link evaluation in DAPPLE. List of indirect interactors.</p

    Mapping genomic loci implicates genes and synaptic biology in schizophrenia

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    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
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