The effects of sex, age, Alzheimer's disease, and 24-hour activity rhythms on the timing of rhythms of methylation.

Circular histograms of the effect of clinical variables on the timing of the nadir of methylation of 21,282 high amplitude DNA methylation sites, in 1 hour bins. P-values determined using Rao's Test for the equality of polar directions. Dark lines indicate angular means. (A) Female vs. Male Sex. (B) Age above vs. below median (88.4 years). (C) Present vs. absent Alzheimer's Disease based on NIA-Reagan Criteria (intermediate/high = present; low/no = absent). (D) High vs. low actigraphic rhythmicity based on 24-hour activity rhythms determined ante-mortem in a subset of 134 participants by actigraphy and quantified using the interdaily stability metric as described in the text. Female sex, higher age, and absence of dementia were associated with an earlier timing of methylation nadirs.