Population structure of the Caucasian cases and controls.

<p>The red dots represent diTdP cases and blue dots represent controls (drug-exposed patients and population [POPRES] controls). The plot shows the first and second eigen vectors, which clearly separate the Caucasians into a Northwestern group (top) and other groups from Southern and Eastern Europe. The dense cluster on the lower left represents the subjects of Spanish origin from the POPRES collection. The final analysis included subjects with PC1<–0.03.</p

Screening rare variants in congenital long QT Syndrome disease genes in 216 diTdP cases.

<p>Screening rare variants in congenital long QT Syndrome disease genes in 216 diTdP cases.</p

QQ plot of the results from logistic regression on the Northwestern European cohort.

<p>The x axis is –log10 of the expected P-value and the y axis is –log10 of the observed P-values. Black solid lines denote the null distribution. The bulk of the values (red dots) closely follow the expectation under the null model (black line) showing that there is no significant inflation of test statistic due to factors such as population stratification. The tail end shows significant deviation from null model illustrating that there are a few observed significant associations.</p

Minor Allele Frequency (MAF) for rs2276314, the top associated SNP, in different sample sub-groups.

<p>Abbreviations: AF (atrial fibrillation), MAF (minor allele frequency).</p

diTdP Genome-Wide Association Study: top associated SNPs.

<p>Abbreviations: OR (Odds Ratio, OR is expressed with a confidence interval of 95%), CHR (chromosome).</p

The effect size (OR) of rs2276314 in different drug-specific groups.

<p>The numbers in parentheses are the numbers of cases for each group. The horizontal blue lines mark the 95% confidence interval of odds ratios.</p

diTdP Genome-Wide Association Study: Demographic and clinical characteristics of the enrolled cases summarized by cohort.

*<p>In total, 66% of the Leducq cases self-declared ethnicity, among then 92% (61% of total) are Europeans.</p

diTdP Northwestern European cohort: causal drugs and demographic and clinical characteristics of the diTdP Northwestern European cases summarized by drug group.

<p>Subjects might have experienced diTdP due to more than one causal drug.</p

Genetic risk score GRS_<i>GWAS</i> for schizophrenia.

<p>The <i>x-</i>axis shows the effect size for the 15 SNPs for which data were available in the PGC schizophrenia dataset comprising the GRS_<i>GWAS</i> influencing levels of CRP, with corresponding standard error bars. The <i>y-</i>axis shows the log OR of the GRS_<i>GWAS</i> SNPs for schizophrenia (SCZ) with corresponding standard error bars. The effect estimate of CRP level on disease risk is represented by the red solid line, with gradient α. The 95% CI of this α estimate is represented by the grey dashed lines. The included SNPs are shown by Arabic numbering: #1, rs2847281 (gene: <i>PTPN2</i>; chromosome: 18; basepair position: 12811593); #2, rs340029 (<i>RORA</i>; 15; 58682257); #3, rs6901250 (<i>GPRC6A</i>; 6; 117220718); #4, rs10745954 (<i>ASCL1</i>; 12; 102007224); #5, rs4705952 (<i>IRF1</i>; 5; 131867517); #6, rs12037222 (<i>PABPC4</i>; 1; 39837548); #7, rs12239046 (<i>NLRP3</i>; 1; 245668218); #8, rs6734238 (<i>IL1F10</i>; 2; 113557501); #9, rs13233571 (<i>BCL7B</i>; 7; 72609167); #11, rs1260326 (<i>GCKR</i>; 2; 27584444); #12, rs4129267 (<i>IL6R</i>; 1; 152692888); #13, rs1800961 (<i>HNF4A</i>; 20; 42475778); #14, rs4420065 (<i>LEPR</i>; 1; 5934049); #15, rs10521222 (<i>SALL1</i>; 16; 49716211); 12; 119905190); #17, rs2794520 (<i>CRP</i>; 1; 157945440). The three SNPs of #10, rs9987289 (<i>PPP1R3B</i>; 8; 9220768); #16, rs1183910 (<i>HNF1A</i>; and #18, rs4420638 (<i>APOC1</i>; 19; 50114786) were not present in the data of the PGC.</p

The effect of the CRP genetic risk score instrument of 18 SNPs associated with CRP (GRS_<i>GWAS</i>) on somatic and neuropsychiatric outcomes.

<p>The effect of the CRP genetic risk score instrument of 18 SNPs associated with CRP (GRS_<i>GWAS</i>) on somatic and neuropsychiatric outcomes.</p