Neandertal introgression dissects the genetic landscape of neuropsychiatric disorders and associated behavioral phenotypes

Abstract Background Advances have recently been made in identifying the genetic basis of psychiatric and neurological disorders, however, fundamental questions about their evolutionary origins remain elusive. Here, introgressed variants from archaic humans such as Neandertals can serve as an intriguing research paradigm. Methods We compared the number of associations for Neandertal variants to the number of associations of frequency-matched non-archaic variants with regard to human CNS disorders (neurological and psychiatric), nervous system drug prescriptions as a proxy for disease, and related non-disease phenotypes in the UK biobank (UKBB), the NESDA cohort and the Biobank Japan. Results While no enrichment for Neandertal genetic variants were observed in the UKBB for psychiatric or neurological disease categories, we found significant associations with certain behavioral phenotypes including pain, chronotype/sleep, smoking and alcohol consumptions. Several of these associations were also observed in NESDA and the Biobank Japan, suggesting their evolutionary relevance across different ancestry backgrounds. Intriguingly, in some instances, the enrichment signal was driven by Neandertal variants that represented the strongest association genome-wide. Conclusions Our data suggest that evolutionary processes in recent human evolution like admixture with Neandertals significantly contribute to behavioral phenotypes but not psychiatric and neurological diseases. These findings help to link genetic variants in a population to putative past beneficial effects, which likely only indirectly contribute pathology in modern humans, possibly due to changes in lifestyle and maladaptation.