Human Biology Open Access Pre-Prints

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Ancient human genome data that has accumulated in recent years can be employed to establish the spatiotemporal trajectories of genetic variants associated with human diseases. Such knowledge might illuminate if and how past adaptations impact contemporary human health and medicine. Scarcely any studies have yet been attempted to evaluate the genetic susceptibility to neurodegenerative disorders in ancient human communities. Using publicly available ancient human genome-wide data the present study evaluates the molecular predisposition to neurodegenerative disorders in ancient human communities. To this end we screened the ancient genome-wide data for the presence of variants unequivocally associated with neurodegenerative disorders in modern populations, and their historical and geographic prevalence was assessed. These variants are two rare variants in the LRRK2 gene associated with Mendelian Parkinson's disease, a pathogenic variant in the CRH gene, associated with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), and a rare variant in the TREM2 gene, a possible risk modifier associated with Alzheimer's disease. Our assessment of the historical and geographic prevalence indicates differing spatiotemporal frequency dynamics for these clinically significant variants. Neurodegenerative disorders are often with poorly understood pathogenesis that might be elucidated by studying the interaction of past genetic variability with ecological and evolutionary factors such as adverse environmental conditions, specific selective pressures, periods of population isolation and admixture processes. Data on molecular predisposition to neurodegenerative disorders in ancient genomes is instructive to modern medical diagnostic and therapeutic practices.