Influence of long CAG and age on cerebral gray matter.

<p><b>Note.</b> L, left; R, right;</p><p>*corrected P value at the set level, 0.023.</p

Projections of coronal (upper row) and axial (middle row) slices onto the SPM template as well as maximum intensity projections (lower row) are shown.

<p>MNI coordinates are indicated in the left upper corners. Increasing significance (T score) is color-coded from dark red to light yellow as indicated by the bar in the center. Note that only the clusters marked with a red rectangle contain peak voxels, which remained significant after correction for multiple comparisons at the voxel level. For better visibility, all results (including those from exploratory analyses) are shown at a height threshold of 0.01 uncorrected. Cluster sizes were restricted to 20 contiguous voxels for ROI analyses or subjected to cluster level correction (p<0.05 corrected) for the whole brain analysis. A) Combined effect of long CAG & its interaction with age, ROI analysis (left) and whole-brain analysis (right) revealing one bilateral cluster reaching from the pallidum across parts of the ventral thalamus to the midbrain (corrected P value at the cluster level, 0.003). B) Main effect of the long CAG, ROI analysis. C) Interaction analysis of long CAG with age, ROI analysis.</p

Table_1_Usual dietary intake and change in DNA methylation over years: EWAS in KORA FF4 and KORA fit.xlsx

IntroductionChanges in DNA methylation can increase or suppress the expression of health-relevant genes. We investigated for the first time the relationship between habitual food consumption and changes in DNA methylation.MethodsThe German KORA FF4 and KORA Fit studies were used to study the change in methylation over a median follow-up of 4 years. Only subjects participating in both surveys and with available dietary and methylation data were included in the analysis (n = 465). DNA methylation was measured using the Infinium MethylationEPIC BeadChip (Illumina), resulting in 735,527 shared CpGs across both studies. Generalized estimating equation models with an interaction term of exposure and time point were used to analyze the association of 34 food groups, folic acid, and two dietary patterns with changes in DNA methylation over time.ResultsThe results were corrected for genomic inflation. Significant interaction terms indicate different effects between both time points. We observed only a few significant associations between food intake and change in DNA methylation, except for cream and spirit consumption. The annotated genes include CLN3, PROM1, DLEU7, TLL2, and UGT1A10.DiscussionWe identified weak associations between food consumption and DNA methylation change. The differential results for cream and spirits, both consumed in low quantities, require replication in independent studies.</p

Table_2_Usual dietary intake and change in DNA methylation over years: EWAS in KORA FF4 and KORA fit.xlsx

IntroductionChanges in DNA methylation can increase or suppress the expression of health-relevant genes. We investigated for the first time the relationship between habitual food consumption and changes in DNA methylation.MethodsThe German KORA FF4 and KORA Fit studies were used to study the change in methylation over a median follow-up of 4 years. Only subjects participating in both surveys and with available dietary and methylation data were included in the analysis (n = 465). DNA methylation was measured using the Infinium MethylationEPIC BeadChip (Illumina), resulting in 735,527 shared CpGs across both studies. Generalized estimating equation models with an interaction term of exposure and time point were used to analyze the association of 34 food groups, folic acid, and two dietary patterns with changes in DNA methylation over time.ResultsThe results were corrected for genomic inflation. Significant interaction terms indicate different effects between both time points. We observed only a few significant associations between food intake and change in DNA methylation, except for cream and spirit consumption. The annotated genes include CLN3, PROM1, DLEU7, TLL2, and UGT1A10.DiscussionWe identified weak associations between food consumption and DNA methylation change. The differential results for cream and spirits, both consumed in low quantities, require replication in independent studies.</p

Selected box plots for metabolites of interest for PD (left) and RLS (right).

<p>Selected box plots for metabolites of interest for PD (left) and RLS (right).</p

Ten Rare, Non-synonymous Variants Shared by Individuals IV:11 and IV:18 of Family PARK_0005.

<p>The rare variants common to the two affected individuals were genotyped in 975 cases and 1014 controls. Penetrance with regard to the PD phenotype was assessed in 6 family members belonging to the same generation as the affected individuals. EA = European American.</p

Qualitative multifactorial interaction network of <i>PLXNA4</i> and genetic factors with known and hypothetical relevance to PD.

<p>Edges obtained from CIDeR are highlighted in blue, PD-specific pathways from KEGG are given in green, red edges denote annotations from OMIM and edges extracted from literature, protein-protein interaction databases or high-confidence predictions are colored black. Undirected protein-protein interactions hold circular ends, directed molecular relations are marked by arcs, whereas general regulations have arrows with no filling, activations have filled arrows and inhibitions have blunted end. Dashed lines indicate indirect effects.</p

Assessment of cell viability and subcellular protein localization in fibroblasts.

<p>(A) The presence of <i>PLXNA4</i> p.Ser657Asn do not affect cell viability as assay by live-dead staining and FACS. (B) Immunohistochemistry shows similar subcellular localization of <i>PLXNA4</i> (anti-PLXNA4, Sigma, 1∶500) in fibroblasts with and without the p.Ser657Asn amino acid substitution (scale bar = 50 µm).</p

Pedigree and Linkage Analysis.

<p>(A) Pedigree of family used for exome sequencing. Open symbols indicate unaffected family members, affected individuals are denoted by closed symbols. An arrow denotes the individuals whose exomes were sequenced. Sex was obscured and birth order was altered to protect privacy. A diagonal line indicates a deceased individual. (B) 25 genomic regions on 12 chromosomes with logarithm of the odds (LOD) score≥0.5 were identified by linkage analysis. Green boxes represent genomic regions with LOD≥0.5, yellow stars represent the location of the four candidate genes remaining after frequency assessment (<i>GOLGA4</i>-chr3, <i>PLXNA4</i>-chr7, <i>OGN</i>-chr9, <i>CPNE1</i>-chr20). <i>PLXNA4</i> on chromosome 7 represents the only of the four genes overlapping a genomic region with LOD≥0.5.</p

<i>NPC1/2</i> variant frequencies by group^a.

<p>PD = Parkinson's disease; FTLD = frontotemporal lobar degeneration;</p><p>PSP = progressive supranuclear palsy.</p><p>^a Absolute number of variant carriers, percentage of carriers within the group, <i>p</i> values.</p><p>^b Variants previously described as disease-causing in a NPC patient.</p><p>^c All rare (MAF<1%) variants detected in <i>NPC1</i> and <i>NPC2</i> (synonymous changes omitted).</p