The protocol-defined field activities have now been completed. The field study examinations were started in March 2018 in five study centres in Finland, and ended in February 2020. In total, 7,345 individuals participated in the study: Generation 1 (original YFS cohort members, N=2,128, 66.2% participation rate); Generation 0 (parents of the original cohort members, N=2,460, 62.8%), and Generation 2 (offspring of the original cohort memners, N=2,757, 48.6%). In total, 1,378 sperm samples have been collected for RNA sequencing across three generations of males aged 18 and over.
The data are being used to test the hypothesis that paternal exposures can lead to phenotypic changes in the offspring via non-coding RNA molecules in the semen. As there are no standard approaches for analysing such multigenerational mediation questions, our team of statisticians has devoted considerable efforts in developing statistical framework to examine epigenetic inheritance in a multigenerational setting.
The MULTIEPIGEN project’s preliminary main results thus far represent the most recent advancements in the field of epigenetic inheritance in humans. These can be summarised as follows: First, we observe several anticipated links between paternal exposures and offspring phenotypes. The existence of these associations is the prerequisite for further enquiry into causality. For example, paternal exposure to some organic pollutants is associated with increased risk of obesity and higher serum cholesterol levels in the offspring. In addition, paternal smoking before conception is associated with higher risk of obesity and the metabolic syndrome in the offspring, as well as with higher risk of anxiety. Furthermore, paternal obesity before conception associates with many components of the metabolic syndrome in the offspring. Second, we see that the pre-specified paternal exposures associate with sperm epigenome. For example, exposure to certain organic pollutants during childhood and adolescence is associated with changes in sperm non-coding RNA profile in adulthood. In addition, we see links between increased adiposity and sperm RNA profile – confirming previous studies in humans. Third, we can identify several links between paternal epigenome and offspring phenotype, including cardio-metabolic phenotypes, cognitive function parameters and psychological well-being. Fourth, the preliminary analyses suggest that some epigenetic markers could be candidate carries of the information between the generations. Thus, the results of the MULTIEPIGEN project provide novel observations in support of the hypothesis that non-genetic inheritance may occur in humans.
