MULTIEPIGEN

Ancestral environmental exposures and offspring health – a multigenerational epidemiologic cohort study across 3 generations. The study seeks to solve whether parental exposures to e.g. tobacco smoke and environmental pollutants affect offspring health via epigenetic mechanisms.

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About MULTIEPIGEN

MULTIEPIGEN seeks to solve whether ancestral exposure to various stressors transmit to offspring via epigenetic mechanisms. Specifically, the study aims to provide proof for the hypothesis that paternal stressors can affect offspring phenotype. 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. This implicates 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. It is not possible to perform controlled experiments in humans to study intergenerational transmission of environmental stressors. Additionally, the phenomenon has been scarcely examined in population-based studies because a priori designed cohorts including several generations are lacking. To yield such research platform, MULTIEPIGEN was designed to expand the existing population-based Cardiovascular Risk in Young Finns Study to the parents and offspring of the original participants. Multigenerational epidemiologic data showing links between ancestral exposures and offspring phenotypes that operate via epigenetic mechanisms would provide a conceptual change in the developmental biology in humans and have substantial ramifications on public health.

Study Description

The first extended MULTIEPIGEN follow-up study was conducted from 2018 to 2020 in five study centres in Finland (Turku, Tampere, Helsinki, Kuopio and Oulu). In that study phase, the original participants of the cohort (age range 40-58 years), their offspring (age range 3-38 years), and their parents (age range 59-93 years) were invited. In total, 7,345 individuals participated in the study. MULTIEPIGEN focuses specifically on three key ancestral exposures – tobacco smoke, persistent organic pollutants, and accumulation of psychosocial adversities – that have high plausibility to cause intergenerational effects on obesity-related phenotypes, cognitive function and psychological well-being. To provide understanding on the mechanisms of intergenerational transmission, blood and semen samples were collected for epigenetic marker analysis. Uniquely, MULTIEPIGEN is the first multigenerational large-scale epidemiologic study that has collected germ cells across three generations of males. Additionally, vascular and hepatic ultrasonography has been performed, faecal and hair samples, anthropometric measures, detailed questionnaire data on e.g. lifestyle and diet have been collected. Together these data provide a large-scale population-based data bank that covers three generations.

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Project leader

Olli Raitakari

Academy Professor, Cardiovascular Medicine (CAPC) MD/PhD

Project secretary

Nina Ruotsalainen