Inter-rater agreement and reliability of the assessment of lithium response in the two-stage case-vignette rating procedure: kappa and intra-class correlation analysis.

<p>TS: total score.</p><p>ICC: intra-class correlation.</p><p>CI: confidence interval.</p>*<p>Mixed and random effects models.</p>§<p>70 raters.</p>¶<p>48 raters.</p

Empirical and theoretical distributions of the total score in the Consortium on Lithium Genetics sample.

<p>Frequentist, <b>A</b>, and Bayesian minimum message length, <b>B</b>, mixture modeling identify three subpopulations of non responders (grey), partial responders (red), and full responders (blue) in total scores of 1,308 bipolar disorder patients characterized for response to lithium maintenance treatment.</p

Number of raters from the Consortium on Lithium Genetics (ConLiGen) centres participating in the two-stage case-vignette rating procedure for inter-rater reliability and agreement.

<p>ConLiGen: Consortium on Lithium Genetics.</p>*<p>Hokkaido, Osaka, Tokio, Riken Brain Science Institute.</p

Distribution of total and A scores in the Consortium on Lithium Genetics sample.

<p>Histogram plot of the scale scores in 1,308 bipolar disorder patients characterized for response to lithium maintenance treatment.</p

New genome-wide significant genes associated with AD in the vicinity of recently reported single SNP genome-wide significant hits[9], [19].

<p>Gene-wide p-values are shown for those genes with p<2.5×10⁻⁶ for which the best single-SNP p-value in that gene is greater than 5×10⁻⁸ in the combined Stage 1 and Stage 2 sample. Previously reported genes<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094661#pone.0094661-Harold1" target="_blank">[4]</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094661#pone.0094661-Seshadri1" target="_blank">[8]</a> ± 0.5 Mb around them are excluded.</p><p>Gene-wide p-values in the combined Stage 1 and Stage 2 sample obtained by combining the p-values from the Stage 1 with those from the Stage 2 using Fisher's method. The LD between rs1476679 (chr7∶100,004,446) reported by IGAP <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094661#pone.0094661-Lambert2" target="_blank">[9]</a> and the best SNP in ZNF3 is r² = 0.16. The LD between rs10838725 (chr11: 47,557,871) reported by IGAP <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094661#pone.0094661-Lambert2" target="_blank">[9]</a> and the best SNPs in the region on chr 11 in the table are r² = 0.3 and 0.88 for <i>NDUFS3</i> and <i>MTCH2</i> respectively.</p

Overrepresentation of significant loci, excluding regions of 0.5[4]–[8] and Stage 1 IGAP genes[9], [19] containing genome-wide significant SNPs.

<p>The observed number of genes is calculated by combining significant loci within 0.5 Mb into one signal. The APOE region is excluded (CHR19; 44,411,940–46,411,945bp). The total number of genes after exclusions is 24,849.</p

New genome-wide significant genes associated with AD.

<p>Gene-wide p-values are shown for those genes with p<2.5×10⁻⁶ for which the best single-SNP p-value in that gene is greater than 5×10⁻⁸ in the combined Stage 1 and Stage 2 sample. Previously reported genes<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094661#pone.0094661-Harold1" target="_blank">[4]</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094661#pone.0094661-Seshadri1" target="_blank">[8]</a> ± 0.5 Mb around them are excluded.</p><p>Gene-wide p-values in the combined Stage 1 and Stage 2 sample obtained by combining the p-values from the Stage 1 with those from the Stage 2 using Fisher's method.</p

Linkage disequilibrium structure of <i>TP53INP1</i> gene.

<p>The SNPs which are significant at 10⁻⁴ level are circled in red.</p

Linkage disequilibrium structure of <i>IGHV1-67</i> gene ±5 kb.

<p>The SNPs which are significant at 10⁻⁴ level are circled in red.</p