Neandertal introgression partitions the genetic landscape of neuropsychiatric disorders and associated behavioral phenotypes
Abstract 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 t...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-10-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-022-02196-2 |
| _version_ | 1797996047764553728 |
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| author | Michael Dannemann Yuri Milaneschi Danat Yermakovich Victoria Stiglbauer Hanna Maria Kariis Kristi Krebs Manuel A. Friese Christian Otte Estonian Biobank Research Team Kelli Lehto Brenda W. J. H. Penninx Janet Kelso Stefan M. Gold |
| author_facet | Michael Dannemann Yuri Milaneschi Danat Yermakovich Victoria Stiglbauer Hanna Maria Kariis Kristi Krebs Manuel A. Friese Christian Otte Estonian Biobank Research Team Kelli Lehto Brenda W. J. H. Penninx Janet Kelso Stefan M. Gold |
| author_sort | Michael Dannemann |
| collection | DOAJ |
| description | Abstract 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 |
| first_indexed | 2024-04-11T10:11:15Z |
| format | Article |
| id | doaj.art-fa483aeffa354e6a92ab5192263f8dd7 |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-04-11T10:11:15Z |
| publishDate | 2022-10-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-fa483aeffa354e6a92ab5192263f8dd72022-12-22T04:30:06ZengNature Publishing GroupTranslational Psychiatry2158-31882022-10-0112111010.1038/s41398-022-02196-2Neandertal introgression partitions the genetic landscape of neuropsychiatric disorders and associated behavioral phenotypesMichael Dannemann0Yuri Milaneschi1Danat Yermakovich2Victoria Stiglbauer3Hanna Maria Kariis4Kristi Krebs5Manuel A. Friese6Christian Otte7Estonian Biobank Research TeamKelli Lehto8Brenda W. J. H. Penninx9Janet Kelso10Stefan M. Gold11Institute of Genomics, University of TartuDepartment of Psychiatry, Amsterdam Public Health and Amsterdam Neuroscience, Amsterdam UMC/Vrije UniversiteitInstitute of Genomics, University of TartuCharité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Klinik für Psychiatrie und Psychotherapie, Campus Benjamin FranklinInstitute of Genomics, University of TartuInstitute of Genomics, University of TartuInstitut für Neuroimmunologie und Multiple Sklerose (INIMS), Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg EppendorfCharité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Klinik für Psychiatrie und Psychotherapie, Campus Benjamin FranklinInstitute of Genomics, University of TartuDepartment of Psychiatry, Amsterdam Public Health and Amsterdam Neuroscience, Amsterdam UMC/Vrije UniversiteitMax Planck Institute for Evolutionary AnthropologyCharité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Klinik für Psychiatrie und Psychotherapie, Campus Benjamin FranklinAbstract 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 humanshttps://doi.org/10.1038/s41398-022-02196-2 |
| spellingShingle | Michael Dannemann Yuri Milaneschi Danat Yermakovich Victoria Stiglbauer Hanna Maria Kariis Kristi Krebs Manuel A. Friese Christian Otte Estonian Biobank Research Team Kelli Lehto Brenda W. J. H. Penninx Janet Kelso Stefan M. Gold Neandertal introgression partitions the genetic landscape of neuropsychiatric disorders and associated behavioral phenotypes Translational Psychiatry |
| title | Neandertal introgression partitions the genetic landscape of neuropsychiatric disorders and associated behavioral phenotypes |
| title_full | Neandertal introgression partitions the genetic landscape of neuropsychiatric disorders and associated behavioral phenotypes |
| title_fullStr | Neandertal introgression partitions the genetic landscape of neuropsychiatric disorders and associated behavioral phenotypes |
| title_full_unstemmed | Neandertal introgression partitions the genetic landscape of neuropsychiatric disorders and associated behavioral phenotypes |
| title_short | Neandertal introgression partitions the genetic landscape of neuropsychiatric disorders and associated behavioral phenotypes |
| title_sort | neandertal introgression partitions the genetic landscape of neuropsychiatric disorders and associated behavioral phenotypes |
| url | https://doi.org/10.1038/s41398-022-02196-2 |
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