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

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

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

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

Heat map showing the distribution of whole chromosome arm and focal copy number aberrations across the cohorts.

<p>Sample heterogeneity occurred within cohorts however a focal pattern is evident in the <i>BRAF</i>mut/MSS and a whole arm pattern is present in the <i>BRAF</i>wt/MSS cohort.</p