TY - JOUR
T1 - Neandertal introgression partitions the genetic landscape of neuropsychiatric disorders and associated behavioral phenotypes
AU - Dannemann, Michael
AU - Milaneschi, Yuri
AU - Yermakovich, Danat
AU - Stiglbauer, Victoria
AU - Kariis, Hanna Maria
AU - Krebs, Kristi
AU - Friese, Manuel A.
AU - Otte, Christian
AU - Esko, T. nu
AU - Metspalu, Andres
AU - Milani, Lili
AU - Mägi, Reedik
AU - Nelis, Mari
AU - Lehto, Kelli
AU - Penninx, Brenda W. J. H.
AU - Kelso, Janet
AU - Estonian Biobank Research Team
AU - Gold, Stefan M.
N1 - Funding Information: NESDA: Funding was obtained from the Netherlands Organization for Scientific Research (Geestkracht program grant 10-000-1002); the Center for Medical Systems Biology (CSMB, NWO Genomics), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL), VU University’s Institutes for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam, University Medical Center Groningen, Leiden University Medical Center, National Institutes of Health (NIH, R01D0042157-01A, MH081802, Grand Opportunity grants 1RC2 MH089951 and 1RC2 MH089995). Part of the genotyping and analyses were funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health.Computing was supported by BiG Grid, the Dutch e-Science Grid, which is financially supported by NWO. MD and DY were supported by the European Union through Horizon 2020 Research and Innovation Program under Grant No. 810645 and the European Union through the European Regional Development Fund Project No. MOBEC008. MD and JK have been supported by the Max Planck Society. HMK, KK, KL: The research in the Estonian Biobank was supported by the EU through the European Regional Development Fund (project number 2014-2020.4.01.15-0012), and the Estonian Research Council through grant number PSG615. Open access funding enabled and organized by Projekt DEAL. Publisher Copyright: © 2022, The Author(s).
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Despite advances in identifying the genetic basis of psychiatric and neurological disorders, fundamental questions about their evolutionary origins remain elusive. Here, introgressed variants from archaic humans such as Neandertals can serve as an intriguing research paradigm. 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). 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 consumption. In some instances, the enrichment signal was driven by Neandertal variants that represented the strongest association genome-wide. SNPs within a Neandertal haplotype that was associated with smoking in the UKBB could be replicated in four independent genomics datasets. 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 to pathology in modern day humans.
AB - Despite advances in identifying the genetic basis of psychiatric and neurological disorders, fundamental questions about their evolutionary origins remain elusive. Here, introgressed variants from archaic humans such as Neandertals can serve as an intriguing research paradigm. 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). 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 consumption. In some instances, the enrichment signal was driven by Neandertal variants that represented the strongest association genome-wide. SNPs within a Neandertal haplotype that was associated with smoking in the UKBB could be replicated in four independent genomics datasets. 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 to pathology in modern day humans.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85139295072&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/36198681
UR - http://www.scopus.com/inward/record.url?scp=85139295072&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41398-022-02196-2
DO - https://doi.org/10.1038/s41398-022-02196-2
M3 - Article
C2 - 36198681
SN - 2158-3188
VL - 12
JO - Translational Psychiatry
JF - Translational Psychiatry
IS - 1
M1 - 433
ER -