Risco poligênico para esquizofrenia: do paleolítico ao pós-neolítico

Abstract

This study investigated the evolution of polygenic risk scores (PRS) for schizophrenia in ancient human populations, from the Early Upper Paleolithic to the Post-Neolithic. Genetic data from 13,353 ancient and contemporary individuals were analyzed, focusing on temporal and geographical variations in PRS while controlling for population structure. The results show that PRS were significantly higher during the Paleolithic compared to the Neolithic and Post-Neolithic periods, with marked reductions following the advent of agriculture. Regionally, Africa exhibited the highest average values and the greatest dispersion, while Europe had the lowest values and a more concentrated distribution. Asia, the Americas, and Oceania showed intermediate or variable patterns, with sample size limitations particularly in Oceania. A Random Forest model indicated that time (years before present), continent, and mitochondrial and Y-chromosome haplogroups were the main predictors of PRS variation, with predictive performance varying across continents. Accumulated Local Effects (ALE) analysis reinforced the importance of the temporal dimension in the dynamics of the scores. These findings describe evolutionary patterns in schizophrenia PRS over time and across regions, providing a solid empirical foundation for future investigations into the factors shaping the distribution of genetic variants associated with psychiatric disorders in human populations.