The contribution of Neanderthal introgression and natural selection to neurodegenerative diseases
Humans are thought to be more susceptible to neurodegeneration than equivalently-aged primates. It is not known whether this vulnerability is specific to anatomically-modern humans or shared with other hominids. The contribution of introgressed Neanderthal DNA to neurodegenerative disorders remains...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996123000967 |
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| author | Zhongbo Chen Regina H. Reynolds Antonio F. Pardiñas Sarah A. Gagliano Taliun Wouter van Rheenen Kuang Lin Aleksey Shatunov Emil K. Gustavsson Isabella Fogh Ashley R. Jones Wim Robberecht Philippe Corcia Adriano Chiò Pamela J. Shaw Karen E. Morrison Jan H. Veldink Leonard H. van den Berg Christopher E. Shaw John F. Powell Vincenzo Silani John A. Hardy Henry Houlden Michael J. Owen Martin R. Turner Mina Ryten Ammar Al-Chalabi |
| author_facet | Zhongbo Chen Regina H. Reynolds Antonio F. Pardiñas Sarah A. Gagliano Taliun Wouter van Rheenen Kuang Lin Aleksey Shatunov Emil K. Gustavsson Isabella Fogh Ashley R. Jones Wim Robberecht Philippe Corcia Adriano Chiò Pamela J. Shaw Karen E. Morrison Jan H. Veldink Leonard H. van den Berg Christopher E. Shaw John F. Powell Vincenzo Silani John A. Hardy Henry Houlden Michael J. Owen Martin R. Turner Mina Ryten Ammar Al-Chalabi |
| author_sort | Zhongbo Chen |
| collection | DOAJ |
| description | Humans are thought to be more susceptible to neurodegeneration than equivalently-aged primates. It is not known whether this vulnerability is specific to anatomically-modern humans or shared with other hominids. The contribution of introgressed Neanderthal DNA to neurodegenerative disorders remains uncertain. It is also unclear how common variants associated with neurodegenerative disease risk are maintained by natural selection in the population despite their deleterious effects. In this study, we aimed to quantify the genome-wide contribution of Neanderthal introgression and positive selection to the heritability of complex neurodegenerative disorders to address these questions.We used stratified-linkage disequilibrium score regression to investigate the relationship between five SNP-based signatures of natural selection, reflecting different timepoints of evolution, and genome-wide associated variants of the three most prevalent neurodegenerative disorders: Alzheimer's disease, amyotrophic lateral sclerosis and Parkinson's disease.We found no evidence for enrichment of positively-selected SNPs in the heritability of Alzheimer's disease, amyotrophic lateral sclerosis and Parkinson's disease, suggesting that common deleterious disease variants are unlikely to be maintained by positive selection. There was no enrichment of Neanderthal introgression in the SNP-heritability of these disorders, suggesting that Neanderthal admixture is unlikely to have contributed to disease risk.These findings provide insight into the origins of neurodegenerative disorders within the evolution of Homo sapiens and addresses a long-standing debate, showing that Neanderthal admixture is unlikely to have contributed to common genetic risk of neurodegeneration in anatomically-modern humans. |
| first_indexed | 2024-04-09T18:09:34Z |
| format | Article |
| id | doaj.art-f01fd2a5dcf3454199658ca3a44ca0e9 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-04-09T18:09:34Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-f01fd2a5dcf3454199658ca3a44ca0e92023-04-14T04:18:45ZengElsevierNeurobiology of Disease1095-953X2023-05-01180106082The contribution of Neanderthal introgression and natural selection to neurodegenerative diseasesZhongbo Chen0Regina H. Reynolds1Antonio F. Pardiñas2Sarah A. Gagliano Taliun3Wouter van Rheenen4Kuang Lin5Aleksey Shatunov6Emil K. Gustavsson7Isabella Fogh8Ashley R. Jones9Wim Robberecht10Philippe Corcia11Adriano Chiò12Pamela J. Shaw13Karen E. Morrison14Jan H. Veldink15Leonard H. van den Berg16Christopher E. Shaw17John F. Powell18Vincenzo Silani19John A. Hardy20Henry Houlden21Michael J. Owen22Martin R. Turner23Mina Ryten24Ammar Al-Chalabi25Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London (UCL), London, UK; Department of Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, UCL, London, UK; NIHR Great Ormond Street Hospital Biomedical Research Centre, UCL, London, UKDepartment of Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, UCL, London, UK; NIHR Great Ormond Street Hospital Biomedical Research Centre, UCL, London, UKMRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UKDepartment of Medicine & Department of Neurosciences, Université de Montréal, Montréal, Québec, Canada; Montréal Heart Institute, Montréal, Québec, CanadaDepartment of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, the NetherlandsNuffield Department of Population Health, Oxford University, Oxford, UKDepartment of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UKDepartment of Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, UCL, London, UK; NIHR Great Ormond Street Hospital Biomedical Research Centre, UCL, London, UKDepartment of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UKDepartment of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UKDepartment of Neurology, University Hospital Leuven, Leuven, Belgium; Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease, Leuven, Belgium; Vesalius Research Center, Laboratory of Neurobiology, Leuven, BelgiumALS Center, Department of Neurology, CHRU Bretonneau, Tours, FranceRita Levi Montalcini Department of Neuroscience, ALS Centre, University of Torino, Turin, Italy; Azienda Ospedaliera Universitaria Città della Salute e della Scienza, Torino, ItalyAcademic Neurology Unit, Department of Neuroscience, Faculty of Medicine, Dentistry and Health, University of Sheffield, Sheffield, UKSchool of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UKDepartment of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, the NetherlandsDepartment of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, the NetherlandsDepartment of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UKDepartment of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UKDepartment of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milano, Italy; Department of Pathophysiology and Transplantation, Dino Ferrari Center, Università degli Studi di Milano, 20122 Milano, ItalyDepartment of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London (UCL), London, UK; Reta Lila Weston Institute, Queen Square Institute of Neurology, UCL, London, UK; UK Dementia Research Institute, Queen Square Institute of Neurology, UCL, London, UK; NIHR University College London Hospitals Biomedical Research Centre, London, UK; Institute for Advanced Study, The Hong Kong University of Science and Technology, Hong Kong, SAR, ChinaDepartment of Neuromuscular Disease, Queen Square Institute of Neurology, UCL, London, UKMRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UKNuffield Department of Clinical Neurosciences, Oxford University, Oxford, UKDepartment of Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, UCL, London, UK; NIHR Great Ormond Street Hospital Biomedical Research Centre, UCL, London, UKDepartment of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Corresponding author at: Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King's College London, London SE5 9RX, UK.Humans are thought to be more susceptible to neurodegeneration than equivalently-aged primates. It is not known whether this vulnerability is specific to anatomically-modern humans or shared with other hominids. The contribution of introgressed Neanderthal DNA to neurodegenerative disorders remains uncertain. It is also unclear how common variants associated with neurodegenerative disease risk are maintained by natural selection in the population despite their deleterious effects. In this study, we aimed to quantify the genome-wide contribution of Neanderthal introgression and positive selection to the heritability of complex neurodegenerative disorders to address these questions.We used stratified-linkage disequilibrium score regression to investigate the relationship between five SNP-based signatures of natural selection, reflecting different timepoints of evolution, and genome-wide associated variants of the three most prevalent neurodegenerative disorders: Alzheimer's disease, amyotrophic lateral sclerosis and Parkinson's disease.We found no evidence for enrichment of positively-selected SNPs in the heritability of Alzheimer's disease, amyotrophic lateral sclerosis and Parkinson's disease, suggesting that common deleterious disease variants are unlikely to be maintained by positive selection. There was no enrichment of Neanderthal introgression in the SNP-heritability of these disorders, suggesting that Neanderthal admixture is unlikely to have contributed to disease risk.These findings provide insight into the origins of neurodegenerative disorders within the evolution of Homo sapiens and addresses a long-standing debate, showing that Neanderthal admixture is unlikely to have contributed to common genetic risk of neurodegeneration in anatomically-modern humans.http://www.sciencedirect.com/science/article/pii/S0969996123000967Neurodegenerative diseasesAlzheimer's diseaseParkinson's diseaseAmyotrophic lateral sclerosisGeneticsNeanderthal |
| spellingShingle | Zhongbo Chen Regina H. Reynolds Antonio F. Pardiñas Sarah A. Gagliano Taliun Wouter van Rheenen Kuang Lin Aleksey Shatunov Emil K. Gustavsson Isabella Fogh Ashley R. Jones Wim Robberecht Philippe Corcia Adriano Chiò Pamela J. Shaw Karen E. Morrison Jan H. Veldink Leonard H. van den Berg Christopher E. Shaw John F. Powell Vincenzo Silani John A. Hardy Henry Houlden Michael J. Owen Martin R. Turner Mina Ryten Ammar Al-Chalabi The contribution of Neanderthal introgression and natural selection to neurodegenerative diseases Neurobiology of Disease Neurodegenerative diseases Alzheimer's disease Parkinson's disease Amyotrophic lateral sclerosis Genetics Neanderthal |
| title | The contribution of Neanderthal introgression and natural selection to neurodegenerative diseases |
| title_full | The contribution of Neanderthal introgression and natural selection to neurodegenerative diseases |
| title_fullStr | The contribution of Neanderthal introgression and natural selection to neurodegenerative diseases |
| title_full_unstemmed | The contribution of Neanderthal introgression and natural selection to neurodegenerative diseases |
| title_short | The contribution of Neanderthal introgression and natural selection to neurodegenerative diseases |
| title_sort | contribution of neanderthal introgression and natural selection to neurodegenerative diseases |
| topic | Neurodegenerative diseases Alzheimer's disease Parkinson's disease Amyotrophic lateral sclerosis Genetics Neanderthal |
| url | http://www.sciencedirect.com/science/article/pii/S0969996123000967 |
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