Periodic Reporting for period 3 - MULTIEPIGEN (Ancestral environmental exposures and offspring health – a multigenerational epidemiologic cohort study across 3 generations)
Reporting period: 2020-11-01 to 2022-04-30
MULTIEPIGEN seeks to solve does ancestral exposure to stressors transmit to offspring via epigenetic mechanisms. Thus far animal models have indicated that exposure to certain stressors can lead to phenotypic changes not only in the predisposed individuals, but also in the future generations, such that individuals can acquire phenotypes caused by exposures of their ancestors. Such effects do not involve new DNA mutations, but are transmitted to offspring via epigenetic mechanisms such as the transfer of non-coding RNA molecules in the semen. In humans, intergenerational transmission has been examined extremely little because a priori designed population-based studies across several generations are lacking. To close this gap, we have expanded the well-characterized Cardiovascular Risk in Young Finns Study (YFS) to the parents and offspring of the original YFS participants. We have performed field studies involving N~7000 individuals across 3 generations and will test 3 key ancestral exposures with very high plausibility causing intergenerational effects on obesity-related phenotypes, cognitive function and psychological well-being. The studied exposures are 1) tobacco smoke, 2) organic pollutants, and 3) accumulation of psychosocial adversities. We have collected serum, blood and semen samples for epigenetic marker analysis to provide understanding of the mechanisms of intergenerational transmission in humans. Multigenerational epidemiologic data showing robust links between ancestral exposures and offspring phenotypes that operate with biologically plausible epigenetic mechanism would provide a conceptual change in the developmental biology in humans and have substantial ramifications on public health.
The protocol-defined field activities have now been completed. They field study examinations were started in March 2018 in five study centres in Finland (cities of Turku, Tampere, Helsinki, Kuopio and Oulu), and ended in February 2020. In total, 7,345 individuals participated in the study: G1 N=2,128 (66.2% participation rate); G0 N=2,460 (62.8%), and G2 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. We are presently processing the data and performing laboratory analyses of the collected samples.
MULTIEPIGEN is the first a priori designed epidemiologic study exploring the hypothesis in man that ancestral life experiences acquired in the environment can be inherited by offspring. Is not possible to perform controlled experiments in humans to study intergenerational transmission of environmental stressors. Therefore, measuring ancestral exposures in an existing population sample and expanding the data collections to their first degree relatives is the only realistic way to test this hypothesis in humans in a timely manner. MULTIEPIGEN is the first multigenerational large-scale epidemiologic study that have collected germ cells across three generations of males. The idea of germline inheritance of acquired traits has the potential to increase our understanding of the aetiology of many human diseases that may have originated from environmentally induced transgenerational effects and thus may have widespread medical and social implications. Epidemiologic data showing robust links between ancestral exposures and offspring phenotypes that operate with biologically plausible epigenetic mechanism would give important insights into the developmental biology in humans and provide sufficient evidence to have an impact on health policies with potentially important implications on public health.