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medRxivGenetic & Genomic MedicinePreprint

Prenatal exposure to genocide accelerates epigenetic aging as measured in second-generation clocks among young adults

Glorieuse UwizeyeiD, Luisa Maria RiveraiD, Hannah G. StolrowiD, Brock C. ChristenseniD, Julienne N. RutherfordiD, Zaneta M. ThayeriD

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Abstract

Prenatal exposure to trauma, including genocide and maternal rape, and adverse childhood experiences (ACEs), are associated with lifespan reduction. We evaluated whether prenatal exposure to genocide or genocidal rape, and ACEs among individuals conceived during the 1994 genocide against Tutsi in Rwanda were associated with differences in age acceleration in three first-generation (Horvath, Hannum, PhenoAge) and four second-generation epigenetic aging clocks (GrimAge, DunedinPace, YingDamAge, YingAdaptAge), given the association between biological aging and mortality. No differences in age acceleration were observed with first-generation age clocks. However, age acceleration was associated with prenatal exposure to extreme stress for all second-generation clocks, with the greatest acceleration observed in the genocidal rape conception group. For YingDamAge clock, acceleration effects were strengthened after inclusion of ACEs. We suggest that prenatal trauma exposure is associated with epigenetic age acceleration. Second-generation clocks may more accurately capture these relationships.

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