Nature Genetics

, том 53 , издание 9 , страницы 1276-1282

A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease

Douglas P Wightman ¹

Iris E. Jansen ¹

Jeanne E. Savage ¹

Alexey Shadrin ^{2, 3}

Shahram Bahrami ^{2, 3, 4}

Dominic Holland ⁵

Arvid Rongve ^{6, 7}

Sigrid Børte ^{3, 8, 9}

Bendik S. Winsvold ^{9, 10, 11}

Ole Kristian Drange ^{12, 13}

Amy E. Martinsen ^{3, 9, 10}

Anne Heidi Skogholt ^{9, 14}

Cristen J. Willer ¹⁵

Geir Bråthen ^{16, 17, 18}

Ingunn Bosnes ^{12, 19}

Jonas Bille Nielsen ^{9, 15, 20}

Lars Fritsche ²¹

Laurent Thomas ^{9, 14}

L. Pedersen ¹⁰

Maiken E Gabrielsen ⁹

Marianne Bakke Johnsen ^{3, 8, 9}

Tore Wergeland Meisingset ^{16, 17}

Wei Zhou ^{22, 23}

Petroula Proitsi ²⁴

Angela Hodges ²⁴

Richard L. Dobson ^{25, 26, 27, 28, 29}

Latha Velayudhan ²⁴

Karl Heilbron ³⁰

Adam Auton ³⁰

Michelle Agee ^{31, 32}

Stella Aslibekyan ^{31, 32}

Elizabeth Babalola ³³

Robert K. Bell ³⁴

Jessica Bielenberg ^{33, 35}

Katarzyna Bryc ³⁶

Emily Bullis ³⁶

Briana Cameron ³⁷

Daniella Coker ^{37, 38}

Gabriel Cuellar Partida ³⁷

Devika Dhamija ³⁹

Sayantan Das ^{39, 40}

Sarah L. Elson ^{39, 40}

Teresa Filshtein ^{39, 41}

Kipper Fletez-Brant ^{42, 43, 44, 45}

Pierre Fontanillas ^{44, 45}

Will Freyman ^{12, 19}

Pooja M. Gandhi ^{9, 46}

Barry Hicks ^{3, 9, 10}

David A. Hinds ^{2, 4}

Karen E. Huber ⁴⁷

Ethan M. Jewett ^{16, 18}

Yunxuan Jiang ^{16, 17}

Aaron Kleinman ⁴⁸

Katelyn Kukar ^{49, 50}

Vanessa Lane ^{3, 47}

Keng-Han Lin ^{24, 51}

Maya Lowe ^{3, 48, 52}

Marie K. Luff ^{23, 53, 54}

Jey C Mccreight ³⁶

Matthew H. McIntyre ^{2, 3, 4}

Kimberly F Mcmanus ^{1, 55}

Скрыть аффилиации авторов Показать аффилиации авторов: 55 аффилиаций

Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU Amsterdam, Amsterdam, The Netherlands

Амстердамский свободный университет

Нейронаука Амстердама

NORMENT Centre, University of Oslo, Oslo, Norway |

Institute of clinical medicine, University of Oslo, Oslo, Norway |

⁴

Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway |

⁵

Department of Neurosciences, University of California, San Diego, La Jolla, USA |

⁶

Department of Research and Innovation, Helse Fonna, Haugesund Hospital, Haugesund, Norway |

⁷

The University of Bergen, Institute of Clinical Medicine (K1), Bergen, Norway |

⁸

Research and Communication Unit for Musculoskeletal Health (FORMI), Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway |

⁹

K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway |

¹⁰

Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway |

¹¹

Department of Neurology, Oslo University Hospital, Oslo, Norway |

¹²

Department of Mental Health, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway |

¹³

Division of Mental Health Care, St. Olavs hospital, Trondheim University Hospital, Trondheim, Norway |

¹⁴

Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, TRONDHEIM, Norway |

¹⁵

Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, USA |

¹⁶

Department of Neuromedicine and Movement science, Norwegian University of Science and Technology, Trondheim, Norway |

¹⁷

Department of Neurology and Clinical Neurophysiology, University Hospital of Trondheim, Trondheim, Norway |

¹⁸

Department of Geriatrics, St. Olav’s Hospital, Trondheim University Hospital, Trondheim, Norway |

¹⁹

Department of Psychiatry, Hospital Namsos, Nord-Trøndelag Health Trust, Namsos, Norway |

²⁰

Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark |

²¹

Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, USA |

²²

Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, USA |

²³

Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, USA |

²⁴

Institute of Psychiatry Psychology and Neurosciences, King’s College London, London, UK |

²⁵

Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, UK |

²⁶

NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London, London, UK |

²⁷

Health Data Research UK London, University College London, London, UK

Университетский колледж Лондона

Организация исследования данных здравоохранения в Великобритании

²⁸

Institute of Health Informatics, University College London, London, UK |

²⁹

NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust, London, UK |

³⁰

23andMe Inc., Sunnyvale, USA |

³¹

Division of Genetic Medicine, Department of Medicine Vanderbilt University Medical Center Nashville, Nashville, USA |

³²

Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, USA |

³³

Department of medical epidemiology and biostatistics, Karolinska Institutet, Stockholm, Sweden |

³⁴

Department of Psychology, University of California-Riverside, Riverside, USA |

³⁵

Institute of Gerontology and Aging Research Network – Jönköping (ARN-J), School of Health and Welfare, Jönköping University, Jönköping, Sweden |

³⁶

deCODE genetics/AMGEN, Reykjavik, Iceland |

³⁷

Department of Geriatric Medicine, Landspitali University Hospital, Reykjavik, Iceland |

³⁸

Faculty of medicine, University of Iceland, Reykjavik, Iceland |

³⁹

Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, Centre for Ageing and Health (AGECAP) at the University of Gothenburg, Gothenburg, Sweden |

⁴⁰

Region Västra Götaland, Sahlgrenska University Hospital, Psychiatry, Cognition and Old Age Psychiatry Clinic, Gothenburg, Sweden |

⁴¹

Region Västra Götaland, Sahlgrenska University Hospital, Psychosis Clinic, Gothenburg, Sweden |

⁴²

Department of Neurodegenerative disease, UCL Institute of Neurology, London, UK |

⁴³

UK Dementia Research Institute At UCL, London, UK |

⁴⁴

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy At the University of Gothenburg, Mölndal, Sweden |

⁴⁵

Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden |

⁴⁶

HUNT Research Center, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway |

⁴⁷

Department of Neurology, Akershus University Hospital, LØrenskog, Norway |

⁴⁸

Department of Geriatric medicine, Oslo University Hospital, Oslo, Norway |

⁴⁹

Department of medical genetics, Oslo University Hospital, Oslo, Norway |

⁵⁰

NORMENT, Department of Clinical Science, University of Bergen, Bergen, Norway |

⁵¹

Centre of Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway |

⁵²

Norwegian National Advisory Unit On Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway |

⁵³

Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA |

⁵⁴

Department of Psychiatry and Psychotherapy, Charité–Universitätsmedizin, Berlin, Germany |

⁵⁵

Department of Child and Adolescent Psychiatry and Pediatric Psychology, Section Complex Trait Genetics, Amsterdam Neuroscience, Vrije Universiteit Medical Center, Amsterdam University Medical Center, Amsterdam, the Netherlands

Медицинский центр Амстердамского Свободного Университета

Нейронаука Амстердама

Тип публикации: Journal Article

Дата публикации: 2021-09-07

Springer Nature

Nature Genetics

scimago Q1

wos Q1

БС1

SJR: 16.586

CiteScore: 45.1

Impact factor: 29.0

ISSN: 10614036, 15461718

DOI: 10.1038/s41588-021-00921-z

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PubMed ID: 34493870

Genetics

Краткое описание

Late-onset Alzheimer’s disease is a prevalent age-related polygenic disease that accounts for 50–70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer’s disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer’s disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer’s disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer’s disease to identify further genetic variants that contribute to Alzheimer’s pathology. A genome-wide association study performed in 1,126,563 individuals identifies seven new loci associated with Alzheimer’s disease and implicates microglia and immune cells in late-onset disease.

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Шолз Сонйа

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Университет Джонса Хопкинса

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д.б.н., проф., ч.-к., Российская академия наук

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Population studies

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Национальный медицинский исследовательский центр кардиологии им. ак. Е.И. Чазова Минздрава РФ

Российский национальный исследовательский медицинский университет имени Н. И. Пирогова

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Wightman D. P. et al. A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease // Nature Genetics. 2021. Vol. 53. No. 9. pp. 1276-1282.

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Wightman D. P. et al. A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease // Nature Genetics. 2021. Vol. 53. No. 9. pp. 1276-1282.

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@article{2021_Wightman,

author = {Douglas P Wightman and Iris E. Jansen and Jeanne E. Savage and Alexey Shadrin and Shahram Bahrami and Dominic Holland and Arvid Rongve and Sigrid Børte and Bendik S. Winsvold and Ole Kristian Drange and Amy E. Martinsen and Anne Heidi Skogholt and Cristen J. Willer and Geir Bråthen and Ingunn Bosnes and Jonas Bille Nielsen and Lars Fritsche and Laurent Thomas and L. Pedersen and Maiken E Gabrielsen and Marianne Bakke Johnsen and Tore Wergeland Meisingset and Wei Zhou and Petroula Proitsi and Angela Hodges and Richard L. Dobson and Latha Velayudhan and Karl Heilbron and Adam Auton and Michelle Agee and Stella Aslibekyan and Elizabeth Babalola and Robert K. Bell and Jessica Bielenberg and Katarzyna Bryc and Emily Bullis and Briana Cameron and Daniella Coker and Gabriel Cuellar Partida and Devika Dhamija and Sayantan Das and Sarah L. Elson and Teresa Filshtein and Kipper Fletez-Brant and Pierre Fontanillas and Will Freyman and Pooja M. Gandhi and Barry Hicks and David A. Hinds and Karen E. Huber and others},

title = {A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease},

journal = {Nature Genetics},

year = {2021},

volume = {53},

publisher = {Springer Nature},

month = {sep},

url = {https://doi.org/10.1038/s41588-021-00921-z},

number = {9},

pages = {1276--1282},

doi = {10.1038/s41588-021-00921-z}

}

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Wightman, Douglas P., et al. “A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease.” Nature Genetics, vol. 53, no. 9, Sep. 2021, pp. 1276-1282. https://doi.org/10.1038/s41588-021-00921-z.

Издатель

Springer Nature

Журнал

Nature Genetics

scimago Q1

wos Q1

БС1

SJR

16.586

CiteScore

45.1

Impact factor

29.0

ISSN

10614036 (Print)

15461718 (Electronic)