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

Alzheimer Disease / genetics Genetic Predisposition to Disease / genetics Genome-Wide Association Study Humans Microglia / cytology Multifactorial Inheritance / genetics Polymorphism, Single Nucleotide / genetics Proteins / metabolism Proteolysis Sample Size

Journal

Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904

Informations de publication

Date de publication:
09 2021
Historique:
received: 12 04 2021
accepted: 16 07 2021
entrez: 8 9 2021
pubmed: 9 9 2021
medline: 15 10 2021
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1038/s41588-021-00921-z PMID: 34493870 PMC: PMC10243600
pubmed: 34493870
doi: 10.1038/s41588-021-00921-z
pii: 10.1038/s41588-021-00921-z
pmc: PMC10243600
mid: NIHMS1871222
doi:

Substances chimiques

Proteins 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1276-1282

Subventions

Organisme : NINDS NIH HHS
ID : R01 NS017950
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG054076
Pays : United States
Organisme : NIA NIH HHS
ID : U24 AG021886
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG032984
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG028555
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG017561
Pays : United States
Organisme : Wellcome Trust
ID : 082604/2/07/Z
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : U01 AG016976
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG008724
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL105756
Pays : United States
Organisme : Medical Research Council
ID : 503480
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_17214
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG033193
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG060470
Pays : United States
Organisme : Alzheimer's Society
ID : 171
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : P30 AG066546
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG052409
Pays : United States

Investigateurs

Michelle Agee (M)
Stella Aslibekyan (S)
Elizabeth Babalola (E)
Robert K Bell (RK)
Jessica Bielenberg (J)
Katarzyna Bryc (K)
Emily Bullis (E)
Briana Cameron (B)
Daniella Coker (D)
Gabriel Cuellar Partida (GC)
Devika Dhamija (D)
Sayantan Das (S)
Sarah L Elson (SL)
Teresa Filshtein (T)
Kipper Fletez-Brant (K)
Pierre Fontanillas (P)
Will Freyman (W)
Pooja M Gandhi (PM)
Barry Hicks (B)
David A Hinds (DA)
Karen E Huber (KE)
Ethan M Jewett (EM)
Yunxuan Jiang (Y)
Aaron Kleinman (A)
Katelyn Kukar (K)
Vanessa Lane (V)
Keng-Han Lin (KH)
Maya Lowe (M)
Marie K Luff (MK)
Jey C McCreight (JC)
Matthew H McIntyre (MH)
Kimberly F McManus (KF)
Steven J Micheletti (SJ)
Meghan E Moreno (ME)
Joanna L Mountain (JL)
Sahar V Mozaffari (SV)
Priyanka Nandakumar (P)
Elizabeth S Noblin (ES)
Jared O'Connell (J)
Aaron A Petrakovitz (AA)
G David Poznik (GD)
Morgan Schumacher (M)
Anjali J Shastri (AJ)
Janie F Shelton (JF)
Jingchunzi Shi (J)
Suyash Shringarpure (S)
Chao Tian (C)
Vinh Tran (V)
Joyce Y Tung (JY)
Xin Wang (X)
Wei Wang (W)
Catherine H Weldon (CH)
Peter Wilton (P)

Commentaires et corrections

Type : CommentIn
Type : ErratumIn
Type : ErratumIn

Informations de copyright

© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.

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Auteurs

Douglas P Wightman (DP)

Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU Amsterdam, Amsterdam, the Netherlands.
ORCID: 0000-0003-3377-4806

Iris E Jansen (IE)

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

Jeanne E Savage (JE)

Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU Amsterdam, Amsterdam, the Netherlands.
ORCID: 0000-0002-2034-8341

Alexey A Shadrin (AA)

NORMENT Centre, University of Oslo, Oslo, Norway.
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
ORCID: 0000-0002-7467-250X

Shahram Bahrami (S)

NORMENT Centre, University of Oslo, Oslo, Norway.
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.

Dominic Holland (D)

Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.

Arvid Rongve (A)

Department of Research and Innovation, Helse Fonna, Haugesund Hospital, Haugesund, Norway.
The University of Bergen, Institute of Clinical Medicine (K1), Bergen, Norway.
ORCID: 0000-0002-0476-4134

Sigrid Børte (S)

Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Research and Communication Unit for Musculoskeletal Health (FORMI), Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway.
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.
ORCID: 0000-0001-9540-3256

Bendik S Winsvold (BS)

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.
Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway.
Department of Neurology, Oslo University Hospital, Oslo, Norway.
ORCID: 0000-0003-4171-8919

Ole Kristian Drange (OK)

Department of Mental Health, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
Division of Mental Health Care, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.

Amy E Martinsen (AE)

Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
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.
Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway.

Anne Heidi Skogholt (AH)

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.
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.

Cristen Willer (C)

Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA.
ORCID: 0000-0001-5645-4966

Geir Bråthen (G)

Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Neurology and Clinical Neurophysiology, University Hospital of Trondheim, Trondheim, Norway.
Department of Geriatrics, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway.
ORCID: 0000-0003-3224-7983

Ingunn Bosnes (I)

Department of Mental Health, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Psychiatry, Hospital Namsos, Nord-Trøndelag Health Trust, Namsos, Norway.

Jonas Bille Nielsen (JB)

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.
Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA.
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.

Lars G Fritsche (LG)

Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
ORCID: 0000-0002-2110-1690

Laurent F Thomas (LF)

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.
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
ORCID: 0000-0003-0548-2486

Linda M Pedersen (LM)

Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway.
ORCID: 0000-0002-8448-983X

Maiken E Gabrielsen (ME)

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.

Marianne Bakke Johnsen (MB)

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

Tore Wergeland Meisingset (TW)

Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Neurology and Clinical Neurophysiology, University Hospital of Trondheim, Trondheim, Norway.

Wei Zhou (W)

Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
ORCID: 0000-0001-7719-0859

Petroula Proitsi (P)

Institute of Psychiatry Psychology and Neurosciences, King's College London, London, UK.
ORCID: 0000-0002-2553-6974

Angela Hodges (A)

Institute of Psychiatry Psychology and Neurosciences, King's College London, London, UK.
ORCID: 0000-0002-5565-6678

Richard Dobson (R)

Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK.
NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, London, UK.
Health Data Research UK London, University College London, London, UK.
Institute of Health Informatics, University College London, London, UK.
NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust, London, UK.
ORCID: 0000-0003-4224-9245

Latha Velayudhan (L)

Institute of Psychiatry Psychology and Neurosciences, King's College London, London, UK.
ORCID: 0000-0002-7712-930X

Karl Heilbron (K)

23andMe Inc., Sunnyvale, CA, USA.

Adam Auton (A)

23andMe Inc., Sunnyvale, CA, USA.

Julia M Sealock (JM)

Division of Genetic Medicine, Department of Medicine Vanderbilt University Medical Center Nashville, Nashville, TN, USA.
Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
ORCID: 0000-0002-9346-3498

Lea K Davis (LK)

Division of Genetic Medicine, Department of Medicine Vanderbilt University Medical Center Nashville, Nashville, TN, USA.
Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
ORCID: 0000-0001-5143-2282

Nancy L Pedersen (NL)

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Chandra A Reynolds (CA)

Department of Psychology, University of California-Riverside, Riverside, CA, USA.
ORCID: 0000-0001-6502-7173

Ida K Karlsson (IK)

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Institute of Gerontology and Aging Research Network - Jönköping (ARN-J), School of Health and Welfare, Jönköping University, Jönköping, Sweden.

Sigurdur Magnusson (S)

deCODE Genetics/Amgen, Reykjavik, Iceland.
ORCID: 0000-0001-6669-3071

Hreinn Stefansson (H)

deCODE Genetics/Amgen, Reykjavik, Iceland.
ORCID: 0000-0002-9331-6666

Steinunn Thordardottir (S)

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

Palmi V Jonsson (PV)

Department of Geriatric Medicine, Landspitali University Hospital, Reykjavik, Iceland.
Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

Jon Snaedal (J)

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

Anna Zettergren (A)

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.
ORCID: 0000-0002-7182-8417

Ingmar Skoog (I)

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

Silke Kern (S)

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

Margda Waern (M)

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

Henrik Zetterberg (H)

Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
UK Dementia Research Institute at UCL, London, UK.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.

Kaj Blennow (K)

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.

Eystein Stordal (E)

Department of Mental Health, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Psychiatry, Hospital Namsos, Nord-Trøndelag Health Trust, Namsos, Norway.
ORCID: 0000-0002-2443-7923

Kristian Hveem (K)

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

John-Anker Zwart (JA)

Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
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.
Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway.
ORCID: 0000-0001-5721-0154

Lavinia Athanasiu (L)

NORMENT Centre, University of Oslo, Oslo, Norway.
Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.

Per Selnes (P)

Department of Neurology, Akershus University Hospital, Lørenskog, Norway.

Ingvild Saltvedt (I)

Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Geriatrics, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway.
ORCID: 0000-0002-7897-9808

Sigrid B Sando (SB)

Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Neurology and Clinical Neurophysiology, University Hospital of Trondheim, Trondheim, Norway.

Ingun Ulstein (I)

Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway.

Srdjan Djurovic (S)

Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
NORMENT, Department of Clinical Science, University of Bergen, Bergen, Norway.
ORCID: 0000-0002-8140-8061

Tormod Fladby (T)

Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Department of Neurology, Akershus University Hospital, Lørenskog, Norway.
ORCID: 0000-0002-9984-9797

Dag Aarsland (D)

Institute of Psychiatry Psychology and Neurosciences, King's College London, London, UK.
Centre of Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.

Geir Selbæk (G)

Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway.
Norwegian National Advisory Unit on Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway.
ORCID: 0000-0001-6511-8219

Stephan Ripke (S)

Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin, Berlin, Germany.
ORCID: 0000-0003-3622-835X

Kari Stefansson (K)

deCODE Genetics/Amgen, Reykjavik, Iceland.
ORCID: 0000-0003-1676-864X

Ole A Andreassen (OA)

NORMENT Centre, University of Oslo, Oslo, Norway.
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
ORCID: 0000-0002-4461-3568

Danielle Posthuma (D)

Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU Amsterdam, Amsterdam, the Netherlands. d.posthuma@vu.nl.
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. d.posthuma@vu.nl.
ORCID: 0000-0001-7582-2365

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Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie d'Alzheimer › A genome-wide association study with 1,126,563...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › A genome-wide association study with 1,126,563...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › A genome-wide association study with 1,126,563...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › A genome-wide association study with 1,126,563...
questionsmedicales.fr › Cellules › Névroglie › Microglie › A genome-wide association study with 1,126,563...
questionsmedicales.fr › Phénomènes génétiques › Modes de transmission héréditaire › Hérédité multifactorielle › A genome-wide association study with 1,126,563...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › A genome-wide association study with 1,126,563...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › A genome-wide association study with 1,126,563...
questionsmedicales.fr › Métabolisme › Protéolyse › A genome-wide association study with 1,126,563...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Méthodologie en recherche épidémiologique › Taille de l'échantillon › A genome-wide association study with 1,126,563...