Male youth BMI is associated with epigenetic ageing of female descendants but not blood or sperm DNA methylation

Studies based on harvest records indicate that grandparental nutrition in youth is associated with the health traits of grandchildren in a sex-specific lineage. We investigated whether male early adulthood anthropometrics associate with epigenetic age, a measure of general well-being, and DNA methylation, a potential molecular inheritance mechanism, in three generations of descendants. Data on weight, height, BMI and chest circumference measured at military draft examinations (at age 18-24 yrs.) were retrieved from national archives for 1,013 men, herein referred to as Generation Archives (G A ). The genome-wide DNA methylation of their descendants participating in the Young Finns Study (YFS) was measured from the blood and sperm from the children (59-80 yrs., n blood = 362, n sperm = 51), grandchildren (34-49 yrs., n blood = 421, n sperm = 98) and great-grandchildren (7-30 yrs., n blood = 200). The men's (G A ) BMI had an inverse association with the epigenetic pace of ageing (DunedinPACE) of their daughters (β = -0.01, p = 0.002, n = 169) and the daughters' daughters (β = -0.01, p = 0.049, n = 126) but not with that of their male descendants. From within the YFS cohort, maternal, but not paternal, BMI at ages 13-34 also had an inverse association with the DunedinPACE of the immediate offspring. However, robust evidence for the inheritance mechanism was not found in the analyses between the anthropometric measurements of the G A men and the DNA methylation profiles in the blood and sperm of their descendants.