Susceptibility to Neurodegenerative Disorders: Insights from Paleogenomic Data

Abstract

Ancient human genome data 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 attempted to evaluate genetic susceptibility to neurodegenerative disorders in ancient human communities. Using publicly available ancient human genome-wide data, this study evaluated the molecular predisposition to neurodegenerative disorders in ancient human communities. Ancient genome-wide data was screened for the presence of variants unequivocally associated with neurodegenerative disorders in modern populations, identifying two rare variants in the LRRK2 gene associated with Mendelian Parkinson’s disease, a pathogenic variant in the CRH gene associated with an uncommon form of epilepsy, and a rare variant in the TREM2 gene that is a possible risk modifier associated with Alzheimer’s disease. Their historical and geographic prevalence was also assessed, indicating differing spatiotemporal frequency dynamics for these clinically significant variants. Neurodegenerative disorders often have 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.