Study Design.

<p>Study Design.</p

RLS-associated SNPs representing <i>cis</i>-eQTLs in peripheral blood.

<p>A total of 23 <i>cis</i>-eQTLs were found in both KORA F4 and SHIP-TREND at p_nominal<1×10⁻³. SNPs which were carried into the replication phase are printed in bold. NS = not significant.</p

Functional gene enrichment and network analysis.

<p>Significant gene-set enrichments on 329 genes deleted in GGE patients revealed an enrichment of GRIN2B interacting proteins, genes of the MGI abnormal emotion/affect behaviour annotation and of the GO cognition annotation. Segmental clusters of genes belonging to a gene family were removed. Positional clustering of genes physically linked on a microdeletion is indicated by a slash between the gene symbols.</p><p>Functional gene enrichment and network analysis.</p

Gene-disrupting microdeletions found only in patients with genetic generalised epilepsy.

<p>GGE, genetic generalised epilepsy; CTR: population control; Chr: chromosome, start/end: genomic start and end point of the deleted segment, hg19; ^<i>P</i>-value: type-1 error rate for a χ2-test with df = 1; OR, 95%-CI, odds ratio with 95% confidence interval. Disease phenotype: ASD: autism spectrum disorder, ADHD: attention deficit hyperactivity disorder, AN: anorexia nervosa, AUT: autism, BPD: bipolar disorder, EE: epileptic encephalopathy, EPI: epilepsy, ID: intellectual disability, MCP: microcephaly, SCZ: schizophrenia; GGE syndromes: CAE: childhood absence epilepsy, JAE: juvenile absence epilepsy, JME: juvenile myoclonic epilepsy, EGMA: epilepsy with generalised tonic-clonic seizures alone predominantly on awakening, EGTCS: epilepsy with generalised tonic-clonic seizures alone, gsw: generalised spike and wave discharges on the electroencephalogram, number/: age-at-onset of afebrile generalised seizures. # previously published in [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005226#pgen.1005226.ref026" target="_blank">26</a>] and * [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005226#pgen.1005226.ref027" target="_blank">27</a>]. Bold gene symbols indicate genes previously implicated in epileptogenesis.</p><p>Gene-disrupting microdeletions found only in patients with genetic generalised epilepsy.</p

Forest plots of the HR of the combined endpoint per one SD of average mean CCA-IMT (with 95% CIs).

<p>Panel I: Group A (asymptomatic individuals with three or more CVD risk factors), HR adjusted for age, sex and annual mean CCA-IMT change (model 1). Panel II: Group A (asymptomatic individuals with three or more CVD risk factors), HR adjusted for age, sex, annual mean CCA-IMT change and other CVD risk factors (model 2). Panel III: Group B (asymptomatic individuals with carotid plaques), HR adjusted for age, sex and annual mean CCA-IMT change (model 1). Panel IV: Group B (asymptomatic individuals with carotid plaques), HR adjusted for age, sex, annual mean CCA-IMT change and other CVD risk factors (model 2). Panel V: Group C (individuals with previous CVD events), HR adjusted for age, sex and annual mean CCA-IMT change (model 1). Panel VI: Group C (individuals with previous CVD events), HR adjusted for age, sex, annual mean CCA-IMT change and other CVD risk factors (model 2).</p

Meta-regression plot for the HR (combined endpoint) per SD of annual mean CCA-IMT change (model 1), by the correlation of baseline and follow-up common CIMT.

<p>The size of each circle represents the precision of the log HR.</p

Cohorts and subsamples.

<p>Cohorts and subsamples.</p

Forest plots of the HR of the combined endpoint per one SD of annual mean CCA-IMT change (with 95% CIs).

<p>Panel I: Group A (asymptomatic individuals with three or more CVD risk factors), HR adjusted for age, sex and average mean CCA-IMT (model 1). Panel II: Group A (asymptomatic individuals with three or more CVD risk factors), HR adjusted for age, sex, average mean CCA-IMT and other CVD risk factors (model 2). Panel III: Group B (asymptomatic individuals with carotid plaques), HR adjusted for age, sex and average mean CCA-IMT (model 1). Panel IV: Group B (asymptomatic individuals with carotid plaques), HR adjusted for age, sex, average mean CCA-IMT and other CVD risk factors (model 2). Panel V: Group C (individuals with previous CVD events), HR adjusted for age, sex and average mean CCA-IMT (model 1). Panel VI: Group C (individuals with previous CVD events), HR adjusted for age, sex, average mean CCA-IMT and other CVD risk factors (model 2).</p

Inclusion criteria.

<p>Inclusion criteria.</p