22 research outputs found

    Histograms of absolute z-scores for bipolar disorder (BD, top panels) and schizophrenia (SCZ, bottom panels) for z-scores ≥3.

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    <p>Left panels are actual data, whereas right panels are hypothetical realizations from a doubling of effective sample size, generated from mixture model fits of f(z) = π<sub>0</sub>f<sub>0</sub>(z)+(1−π<sub>0</sub>)f<sub>1</sub>(z) (see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003455#pgen.1003455.s009" target="_blank">Text S1</a>). Black lines are null sub-densities π<sub>0</sub>f<sub>0</sub>(z) and red lines are the full mixture densities f(z). The local false discovery rate is the ratio fdr = π<sub>0</sub>f<sub>0</sub>(z)/f(z). Vertical black bars in each plot indicate the cut-points where local fdr≤0.05.</p

    “Conditional Manhattan plot” of conditional −log<sub>10</sub> (FDR) values for Bipolar disorder (BD) alone (black) and BD given schizophrenia (SCZ; BD|SCZ, blue).

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    <p>SNPs with conditional −log<sub>10</sub> FDR>1.3 (i.e. FDR<0.05) are shown with large points. A black line around the large points indicates the most significant SNP in each LD block and this SNP was annotated with the closest gene, which is listed above the symbols in each locus. The figure shows the localization of significant loci. Details about the loci are provided in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003455#pgen-1003455-t002" target="_blank">Table 2</a>.</p

    Conjunction FDR; pleiotropic loci in SCZ and BD (SCZ&BD).

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    <p>Independent complex or single gene loci (r<sup>2</sup><0.2) with SNP(s) with a conjunctional FDR (conjFDR)<0.05 in schizophrenia (SCZ) <i>and</i> bipolar disorder (BD). All SNPs with a conjFDR value<0.05 (bidirectional association, i.e. association with SCZ given association with BD (condFDR<0.05) and association with BD given association with SCZ (condFDR<0.05)) are listed and sorted in each LD block. We defined the most significant SNP in each LD block based on the minimum conjFDR. All independent loci are listed consecutively, and the same locus number are used as in the condFDR<0.05 results (<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003455#pgen-1003455-t001" target="_blank">Table 1</a>). Chromosome (Chr). Z-scores for each pleiotropic locus are provided, with minor allele (A1) and major allele (A2). All data were first corrected for genomic inflation.</p>†<p>Same locus identified in previous BD or SCZ genome-wide association studies.</p

    Stratified Q–Q plot and Stratified True Discovery Rate plots.

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    <p><i>Upper panel:</i> Stratified Q-Q plot of nominal versus empirical −log<sub>10</sub> p-values (corrected for inflation) in A) schizophrenia (SCZ) below the standard GWAS threshold of p<5×10<sup>−8</sup> as a function of significance of the association with bipolar disorder (BD) at the level of −log<sub>10</sub>(p)>0, −log<sub>10</sub>(p)>1, −log<sub>10</sub>(p)>2, −log<sub>10</sub>(p)>3 corresponding to p<1, p<0.1, p<0.01, p<0.001, respectively, and in B) BD below the standard GWAS threshold of p<5×10<sup>−8</sup> as a function of significance of association with SCZ at the level of −log<sub>10</sub>(p)>0, −log<sub>10</sub>(p)>1, −log<sub>10</sub>(p)>2, −log<sub>10</sub>(p)>3 corresponding to p<1, p<0.1, p<0.01, p<0.001, respectively. Dotted lines indicate the null-hypothesis. <i>Lower panel:</i> Stratified True Discovery Rate (TDR) plots illustrating the increase in TDR associated with increased pleiotropic enrichment in C) SCZ conditional on nominal BD p-values (SCZ|BD), and D) BD conditional on nominal SCZ p-values (BD|SCZ). For more information about QQ plots, see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003455#pgen.1003455.s009" target="_blank">Text S1</a>.</p

    ROC curves for bipolar disorder (top) and schizophrenia (bottom).

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    <p>Solid black line show the proportion of non-null SNPs declared significant (sensitivity) for a given local false discovery rate (1-specificity). The corresponding ROC curves for bipolar disorder local FDR conditional on schizophrenia (top) and schizophrenia local FDR conditional on bipolar disorder (bottom) are given in red. Power resulting from a hypothetical doubling of effective subject sample size is given by the dashed black lines.</p

    Conditional FDR; SCZ loci given BD (SCZ|BD).

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    <p>Independent complex or single gene loci (r<sup>2</sup><0.2) with SNP(s) with a conditional FDR (condFDR)<0.05 in schizophrenia (SCZ) given the association in bipolar disorder (BD). We defined the most significant SCZ SNP in each LD block based on the minimum condFDR for BD. The most significant SNPs in each LD block are listed. All loci with SNPs with condFDR<0.05 were used to define the number of the loci. Chromosome location (Chr). SCZ FDR values<0.05 are in bold.</p>†<p>Same locus identified in previous SCZ genome-wide association studies. All data were first corrected for genomic inflation.</p

    Conditional FDR; BD loci given SCZ (BD|SCZ).

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    <p>For the independent complex or single gene loci (r<sup>2</sup><0.2) with SNP(s) with a conditional FDR (condFDR)<0.05 in bipolar disorder (BD) given association with schizophrenia (SCZ). All independent loci are listed consecutively. Chromosome location (Chr). All data were first corrected for genomic inflation. BD FDR values<0.05 are in bold.</p>†<p>Same locus identified in previous BD genome-wide association studies.</p

    “Conditional Manhattan plot” of conditional −log<sub>10</sub> (FDR) values for schizophrenia (SCZ) alone (black) and SCZ given bipolar disorder (BD; SCZ|BD, red).

    No full text
    <p>SNPs with conditional −log<sub>10</sub> FDR>1.3 (i.e. FDR<0.05) are shown with large points. A black line around the large points indicates the most significant SNP in each LD block and this SNP was annotated with the closest gene, which is listed above the symbols in each locus. The figure shows the localization of significant loci. Details about the loci are provided in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003455#pgen-1003455-t001" target="_blank">Table 1</a>.</p

    Relative importance of sources for enrichment.

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    <p>The relative importance of different sources of enrichment (x axis) for explaining SNP association with schizophrenia was measured by the Nagelkerke’s R<sup>2</sup>. The enrichment sources were: total linkage disequilibrium (TLD); the squared z-scores of SNP association with bipolar disorder (BIP); the LD weighted genomic annotation scores (Annot); and the heterozygosity (H).</p

    Mean replication z-score and replication rate stratified by enrichment scores.

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    <p>A.) The observed (solid lines) and predicted (dotted lines) mean z-scores in the replication sample (y axis) were plotted against the z-scores in the discovery sample (x axis). The shrinkage of replication z-scores is differentiated by disjoint intervals of relative enrichment scores. B.) The observed (solid lines) and predicted (dotted lines) replication probabilities were plotted against the negative common logarithm of nominal p values of schizophrenia SNPs in discovery sample (x axis). Colors indicate the 10 disjoint intervals of relative enrichment scores, ranging from the least enriched (Bin1) to the most enriched (Bin10). All data were generated by randomly assigning 26 of the PGC schizophrenia sub-studies as discovery sample and 26 as replication sample (split half). The averaged value over 500 iterations was shown.</p
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