Fig. 1

Overview of the methodology used in this study. A: The amount of mitochondrial DNA in circulating blood cells was determined from the Exome sequencing reads mapping to the autosome and the mitochondria. Less mitochondrial DNA (mtDNA) abundance results in fewer MT specific reads compared to autosomal reads. B: Environmental, lifestyle, genetic or metabolomic markers can influence three aspects of the seasonal pattern in mtDNA abundance: A change in amplitude would increase the difference between the minimum and maximum value observed across each year. In contrast, markers influencing the acrophase would result in the whole seasonal pattern shifted by a certain amount of time. Displacement describes the effect that the baseline level is shifted while not influencing the overall cosine pattern. This is equivalent to looking for markers that influence overall mtDNA levels, as was done in previous studies. C: We used linear regression models to investigate the effects of markers on amplitude or acrophase. In case a marker reduces the amplitude, the interaction term (grey) in the regression model would be negative and quantifies the difference between the amplitude observed with (orange) and without the marker present (blue)