Protein coding genes in genomic regions of CNVs detected in HAB/LAB and CD-1 mice.

<p>All genes listed overlap both CNVs in HAB/LAB mice detected with aCGH, JaxMDGA and NGS, and CNVs in CD-1 mice which were best associated with the time the animals spent on the open arm of the EPM (nominal <i>p</i>-value < 0.1).</p><p>Protein coding genes in genomic regions of CNVs detected in HAB/LAB and CD-1 mice.</p

Distribution of CNVs in CD-1 mice.

<p>Chromosomes are indicated by grey horizontal lines. Start points of CNVs are marked by dots and lines are drawn to the end points. Due to limitations in resolution, a small CNV might appear as dot only. CNVs highlighted in blue or red were associated with anxiety-related behavior (time on the open arm of the EPM) with a nominal <i>p</i>-value less than 0.1 or 0.05, respectively.</p

Association of copy number with anxiety-related behavior in CD-1 mice.

<p>Exemplarily, data of three associations resulting in nominal <i>p</i>-values reaching significance (<i>p</i> < 0.05), a trend (<i>p</i> < 0.1), and not reaching significance (<i>p</i> > 0.05), respectively, are shown. Each dot represents data of a single animal (N = 64). The relative copy number is represented by the mean normalized intensities of JaxMDGA probes within the respective CNV. <b>(A)</b> CNV no. 498; <i>P</i>_nom = 0.0009; regression line: y = 0.0091x + 9.4389. <b>(B)</b> CNV no. 164; <i>P</i>_nom = 0.0554; regression line: y = 0.0061x + 10.201. <b>(C)</b> CNV no. 453; <i>P</i>_nom = 0.9791; regression line: y = 0.0008x + 9.6225.</p

Genomic positions of CNVs on chromosome 3.

<p>The chromosome is indicated by a thick horizontal line (grey). Depending on the detection method, CNVs in HAB/LAB mice are depicted in orange (aCGH), dark red (JaxMDGA) and red (NGS), respectively. Data displayed above the grey line represent a copy number gain in HAB vs. LAB animals, data below a copy number loss. Data printed on the grey line show CNVs in 64 CD-1 mice, with those highlighted in color that could be associated with anxiety-related behavior (time on the open arm of EPM) with a nominal <i>p</i>-value less than 0.1 (light blue) or less than 0.05 (blue). Start points of CNVs are marked by dots and lines are drawn to the end points.</p

The top 20 interaction terms after case-control studies in RS-I, RS-II and RS-III separate and combined.

<p>The interactions are sorted based on the <i>p</i>-value of the β_int after the case-control study in the combined data set of RS-I, RS-II and RS-III. The HDL levels are adjusted for sex and age, the residuals are not scaled around zero. Number of cases: 416 (RS-I), 244 (RS-II) and 447 (RS-III). Number of controls: 2996 (RS-I), 1602 (RS-II) and 1621 (RS-III). *1–*4 mark the interaction terms that are in high LD with each other: <i>R</i>²>0.913.</p><p>The top 20 interaction terms after case-control studies in RS-I, RS-II and RS-III separate and combined.</p

The forest plots for β_int of the four most significant interaction terms after meta-analysis of the replication cohorts: rs2315598-rs2853228 (a), rs6848132-rs7863451 (b), rs3756856-rs11758333 (c) and rs4596126-rs11676467 (d).

<p>Although the analysis in the discovery and the filtering was done with scaled phenotypes, for these forest plots, the HDL levels are not scaled in the Rotterdam Study cohorts.</p

The overlap between the interaction terms with <i>p</i>-value<3.03 · 10⁻⁷ after a GWIS with GLIDE in RS-I only and after a GWIS with GLIDE in RS-I, RS-II and RS-III combined.

<p>The overlap between the interaction terms with <i>p</i>-value<3.03 · 10⁻⁷ after a GWIS with GLIDE in RS-I only and after a GWIS with GLIDE in RS-I, RS-II and RS-III combined.</p

Flow diagram overview of the analysis plan.

<p>Flow diagram overview of the analysis plan.</p

The top 20 interaction terms after replication.

<p>The interactions are sorted based on the <i>p</i>-value of the interaction term β_int. The HDL levels are adjusted for sex and age. The phenotypes of the Rotterdam Study are not scaled around zero.</p><p>*Interaction terms in LD with each other (<i>R</i>²>0.872).</p><p>**order of the directions: AGES, ARIC, CHS, ERF, FHS, NFBC-66, RS-I, RS-II, RS-III. The meta-analysis was done with fixed effects.</p><p>The top 20 interaction terms after replication.</p

Baseline characteristics for discovery and replication cohorts.

<p>Baseline characteristics for discovery and replication cohorts.</p