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Fig. 3 | BMC Genomics

Fig. 3

From: Accelerated hematopoietic mitotic aging measured by DNA methylation, blood cell lineage, and Parkinson’s disease

Fig. 3

(A) Correlations between AccelEpiTOC, DNAm measures of blood cell composition, and other DNAm age acceleration measures in PEG, based on DNAm from whole blood (n = 807). Correlations with |R| ≥ 0.25 included as text

(B & C) Results from a logistic regression, with AccelEpiTOC predicting PD. (B) Model 1: PD association for AccelEpiTOC, adjusting for measures of blood cell composition (all blood cell estimates per SD) and other covariates (below) with. (C) Model 2: PD association for AccelEpiTOC and DNAm epigenetic age measures, adjusting for blood cell composition (all blood cell estimates per SD) and other covariates. For both models, all terms are included in the same logistic regression model, also adjusting for age, sex, smoking history, AIMs derived ancestry (European/Hispanic ancestry), and two PCs for DNAm technical variation. The epigenetic mitotic age acceleration (AccelEpiTOC) was centered around zero and scaled per SD. (D) Epigenetic mitotic age acceleration and signs of PD symptom progression: predicted change on MMSE, UPDRS-III; and the Tremor UPDRS-III sub-score over follow-up at two levels of AccelEpiTOC (± 2 SD from mean (0)). The y-axis displays the predicted value of the three exam measures, including MMSE (higher score indicates higher cognitive performance), UPDRS-III (higher score indicates more motor symptoms, assessed by neurologist), and UPDRS-III tremor (tremor sub-score of the UPDRS III; higher score indicates more tremor motor symptoms). Analysis based on symptom progression among PD patients only. Results based on linear repeated measures mixed models including an interaction between epigenetic mitotic aging and time to assess how epigenetic mitotic aging influences change on the exams over time. Models control for age, sex, smoking history, race/ethnicity (AIMs derived European/Hispanic ancestry), PEG study wave, PD duration at baseline, measures of blood cell composition (CD8.naive, CD8pCD28nCD45Ran, plasmablast, CD8 + T cells, B cells, monocytes, and granulocytes), and the two PCs for DNAm technical variation. β (SE) term shown: interaction between AccelEpiTOC*time, representing yearly change on predicted exam score according to AccelEpiTOC. Epigenetic mitotic age acceleration (AccelEpiTOC) was centered around zero and scaled per SD

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