Seasonal variation in cell count.

<p>The seasonal variation of five cells that demonstrate significant seasonal variation. The black lines represent the fitted values in a cosinor regression. The red lines represent the actual cell values. From these figures it is evident that the cells follow complex repeating patterns of peaks and troughs throughout the year. However, it can be observed that they show a consistent seasonal trend following one clear peak and trough per year. These values were collected over a three year period and are plotted in sequential order. The year of collection is labeled in the axis as a number (5–8) after the month. This corresponds to the years 2005, 2006, 2007 and 2008 respectively.</p

Seasonal Effects on Gene Expression

<div><p>Many health conditions, ranging from psychiatric disorders to cardiovascular disease, display notable seasonal variation in severity and onset. In order to understand the molecular processes underlying this phenomenon, we have examined seasonal variation in the transcriptome of 606 healthy individuals. We show that 74 transcripts associated with a 12-month seasonal cycle were enriched for processes involved in DNA repair and binding. An additional 94 transcripts demonstrated significant seasonal variability that was largely influenced by blood cell count levels. These transcripts were enriched for immune function, protein production, and specific cellular markers for lymphocytes. Accordingly, cell counts for erythrocytes, platelets, neutrophils, monocytes, and CD19 cells demonstrated significant association with a 12-month seasonal cycle. These results demonstrate that seasonal variation is an important environmental regulator of gene expression and blood cell composition. Notable changes in leukocyte counts and genes involved in immune function indicate that immune cell physiology varies throughout the year in healthy individuals.</p></div

Gene list enrichment analysis for blood cells.

<p>Enrichment for blood cell signature was found using the userListEnrichment function in the WGCNA R package.</p><p>Gene list enrichment analysis for blood cells.</p

Quantile-quantile plot of observed against expected heterogeneity P-value for allelic associations with HDL-C.

<p>The grey shaded area represents the 95% confidence interval.</p

Descriptive characteristics of genotyped adolescents and adults stratified by sex.

<p>Descriptive characteristics of genotyped adolescents and adults stratified by sex.</p

Quantile-quantile plot of observed against expected heterogeneity P-value for allelic associations with triglycerides.

<p>The grey shaded area represents the 95% confidence interval.</p

Quantile-quantile plot of observed against expected heterogeneity P-value for allelic associations with LDL-C.

<p>The grey shaded area represents the 95% confidence interval.</p

Loci exhibiting adult-adolescent heterogeneity at p<0.05. The locus/phenotype combinations tested were based on the significant associations reported for adults by Teslovich et al.

<p>“Allele/MAF” listed are: major allele, minor allele frequency (MAF). Numbers in “Beta” columns are in SD units, modelled as additive effect of the reference allele.</p

Average number of copy number aberrations (CNAs) and percentage of genome affected per MSS cohort.

<p>A) Average number of CNAs delineated by length per cancer in each MSS cohort. MSS cohorts had a similar number of overall CNAs occurring per cancer, however the <i>BRAF</i>mut/MSS cancers showed a greater number of focal CNAs, with the <i>BRAF</i>wt/MSS cancers having a greater number of whole arm events. <i>BRAF</i>mut/MSI cancers had considerably fewer CNAs of all types. B) Average percentage of genome affected by CNAs delineated by length in each MSS cohort. <i>BRAF</i>wt/MSS cancers had the greatest proportion of genome affected by CNA events, which was due to the higher number of whole arm events in this cohort. <i>BRAF</i>mut/MSS cancers showed a lower proportion of the genome affected by CNAs, which is reflective of the comparably lower rate of whole arm and higher rate of focal events that occurred compared to <i>BRAF</i>wt/MSS cancers.</p

Minimal Common Regions (MCRs) affecting ≥20% of cancers in at least one of the <i>BRAF</i>mut/MSS or <i>BRAF</i>wt/MSS cohorts where differences in CNA frequencies were detected between MSS cohorts.

<p>(Benjamini-Hochberg method applied for adjusted p values).</p