Classification of heart defects (CHD+) according to the distribution frequency of their p-values.

<p>Empirical cumulative distributions of p-values for the 2-by-2 Student tests A: AVSD/ASD; B: AVSD/VSD; C: ASD/VSD. Comparisons were obtained for 11 224 tests. The comparison to the uniform distribution shows that there is no overall differential expression between ASD and VSD (less small p-values than for an uniform distribution). Cdf: cumulative distribution function.</p

Genome-wide association results for natural variation of H₂O₂ release in KORA-GenCord and HapMap cohorts.

<p>Manhattan dot plots show results for genome-wide association analysis for the KORA-GenCord and the HapMap sample cohorts. The blue dots represent the association finding of one single SNP with natural variation in H₂O₂ release. Light and dark blue colors distinguish subsequent chromosomes. We did not analyze genetic markers for mitochondrial SNPs in this study. We show results of a genetic additive model indicating the unadjusted nominal −log₁₀ of p-values. Quantile plots show the observed versus the expected distribution of GWAS for both analyses.</p

GO categories in the CDH⁺ DE genes.

<p>Analysis of the enrichment of GO categories for the genes DE in the comparison between AVSD or ASD+VSD set of genes and CHD⁻ set of genes compared to the genes expressed in LCLs. Analysis used GOrilla software with a p-value threshold at 10⁻³. N - is the total number of genes, B - is the total number of genes associated with a specific null, n - is the number of genes in the group with heart defect, b - is the number of genes in the intersection.</p

Transcriptome signature of heart defects.

<p>Comparison of ratios for DE genes up- or down-regulated in the AVSD or ASD+VSD group between (1) array ratio in the Ts21 CHD⁻ vs 2N, (2) array ratio in CHD⁺ vs CHD⁻, (3) q-PCR ratio from different experiments in CHD⁺ vs CHD⁻ using additional samples (total number in parentheses). Gene nomenclature, <i>AUTS2</i>: autism susceptibility candidate 2; <i>CNN2</i>: calponin 2; <i>DSCR3</i>: Down syndrome critical region gene 3; <i>DYNLT3</i>: dynein, light chain, Tctex-type 3; <i>NQO1</i>: NAD(P)H dehydrogenase, quinone 1; <i>OFD1</i>: oral-facial-digital syndrome 1; <i>PDIA4</i>: protein disulfide isomerase family A, member 4; <i>PIGP</i>: phosphatidylinositol glycan anchor biosynthesis, class P; <i>TTC3</i>: tetratricopeptide repeat domain 3; <i>TUBB2B</i>: tubulin, beta 2B; <i>ACTG1</i>: actin, gamma 1; <i>ALDOC</i>: aldolase C, fructose-bisphosphate; <i>CACYBP</i>: calcyclin binding protein; <i>DTYMK</i>: deoxythymidylate kinase (thymidylate kinase); <i>ENO2</i>: enolase 2 (gamma, neuronal); <i>GART</i>: phosphoribosylglycinamide formyltransferase, phosphoribosylglycinamide synthetase, phosphoribosylaminoimidazole synthetase; <i>IFNAR1</i>: interferon (alpha, beta, and omega) receptor 1; <i>PLTP</i>: phospholipid transfer protein; <i>RPL10A</i>: ribosomal protein L10a; <i>TNFAIP2</i>: tumor necrosis factor, alpha-induced protein 2.</p

Distribution of H₂O₂ release in sample cohorts KORA, GenCord, HapMap and Down Syndrome.

<p>Box plots (in light grey) for the sample cohorts KORA, GenCord, HapMap and Down Syndrome (DS) show the distribution of H₂O₂ variation across cohorts. Each black dot corresponds to an individuals' mean of 4 measures of H₂O₂ release. The median is shown as a dark grey line, the low and upper end of the box plots (in light grey) indicate the first and third quartile of the distribution. The whiskers indicate the lower and upper end of the distribution The distribution of H₂O₂ in the Down Syndrome cohort shows a significant decrease as compared to HapMap (Wilcoxon rank sum test, p<2.88×10⁻¹²).</p

Demographic characteristics for all four population-based cohorts.

<p>Demographic, phenotypic and genotypic characteristics for each cohort are indicated.</p

Results from GWAS for the KORA-GenCord cohort.

<p>We show the results of the top 15 out of the 21 clusters of significantly associated genetic loci (p<5.00×10⁻⁸) and with suggestive associations (p<1.00×10⁻⁵) from genome-wide association analyses. We associated natural variation in H₂O₂ release measured in the KORA-GenCord cohort (n = 279 individuals) with more than 1.4 million markers (called and imputed SNPs). SNP ID, chromosome and position are indicated. Also, the type of SNP, the closest gene (within 1 MB), unadjusted p-value and the number of SNPs per cluster are indicated. SNP annotations were done by using the software WGAViewer (build 36, Ensembl core database <i>homo sapiens core 46 36h</i>, Ensembl variation database <i>homo sapiens variation 46 36h</i>, and Ensembl gene ontology database <i>ensemble go 46</i>).</p

Examples of significant association findings in HapMap GWA.

<p>The significance level (−log₁₀ P) of the top two association findings and two examples of top hits overlapping with either linkage, top GWA in KORA-GenCord, overlap with known candidate genes, or top findings on Hsa21 are shown within a genetic region of 1 Mb ((±500 kb around the significantly associated SNP). The chromosome, SNP ID, location and genic context (RefSeq genes, using UCSC genome browser) are indicated for each depicted SNP.</p

Two significant and two suggestive LOD scores on Hsa12, Hsa15, Hsa1, and Hsa19.

<p>LOD scores of genome-wide linkage analyses using the CEPH-HapMap family-cohort of three generations are plotted for all autosomal chromosomes (in blue). The blue line shows the maximal LOD score within a window size of 10 kb. The red dotted line indicates the significance level identified through 1'000 simulations.</p

Results from GWAS for the HapMap cohort.

<p>Results show the top 15 out of the 90 clusters of significantly associated genetic loci (p<5.00×10⁻⁸) and with suggestive associations (p<1.00×10⁻⁵) from genome-wide association analyses. We associated natural variation in H₂O₂ release measured in the HapMap cohort (n = 58 individuals) with more than 2.2 million markers. SNP ID, chromosome and position are indicated. Also, the type of SNP, the closest gene (within 1 MB), the unadjusted p-value and the number of SNP per cluster are indicated. SNP annotations were done by using the software WGAViewer (build 36, Ensembl core database <i>homo sapiens core 46 36h</i>, Ensembl variation database <i>homo sapiens variation 46 36h</i>, and Ensembl gene ontology database <i>ensemble go 46</i>).</p