Genome-wide association identifies the first risk loci for psychosis in Alzheimer disease.

Alzheimer Disease / genetics Genetic Predisposition to Disease / genetics Genome-Wide Association Study Hallucinations Humans Oxidoreductases Acting on Sulfur Group Donors Polymorphism, Single Nucleotide / genetics Psychotic Disorders / genetics Schizophrenia / genetics

Journal

Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835

Informations de publication

Date de publication:
10 2021
Historique:
received: 04 09 2020
accepted: 29 04 2021
revised: 15 04 2021
pubmed: 12 6 2021
medline: 3 2 2022
entrez: 11 6 2021
Statut: ppublish

Résumé

Psychotic symptoms, defined as the occurrence of delusions or hallucinations, are frequent in Alzheimer disease (AD with psychosis, AD + P). AD + P affects ~50% of individuals with AD, identifies a subgroup with poor outcomes, and is associated with a greater degree of cognitive impairment and depressive symptoms, compared to subjects without psychosis (AD - P). Although the estimated heritability of AD + P is 61%, genetic sources of risk are unknown. We report a genome-wide meta-analysis of 12,317 AD subjects, 5445 AD + P. Results showed common genetic variation accounted for a significant portion of heritability. Two loci, one in ENPP6 (rs9994623, O.R. (95%CI) 1.16 (1.10, 1.22), p = 1.26 × 10

Identifiants

DOI: 10.1038/s41380-021-01152-8 PMID: 34112972 PMC: PMC8660923
pubmed: 34112972
doi: 10.1038/s41380-021-01152-8
pii: 10.1038/s41380-021-01152-8
pmc: PMC8660923
mid: NIHMS1699044
doi:

Substances chimiques

Oxidoreductases Acting on Sulfur Group Donors EC 1.8.-
SUMF1 protein, human EC 3.1.6.-

Types de publication

Journal Article Meta-Analysis Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

5797-5811

Subventions

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 : U24 AG056270
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH057881
Pays : United States
Organisme : Medical Research Council
ID : MR/K013041/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : P30 AG066462
Pays : United States
Organisme : Medical Research Council
ID : G0300429
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG041718
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG067015
Pays : United States
Organisme : Medical Research Council
ID : MR/L501517/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG064877
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_17112
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : R37 MH057881
Pays : United States
Organisme : Medical Research Council
ID : G0902227
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG030653
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG027224
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH116046
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066468
Pays : United States

Informations de copyright

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

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Auteurs

Mary Ann A DeMichele-Sweet (MAA)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
ORCID: 0000-0002-6582-7813

Lambertus Klei (L)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.

Byron Creese (B)

University of Exeter Medical School, College of Medicine and Health, Exeter, UK.
Norwegian, Exeter and King's College Consortium for Genetics of Neuropsychiatric Symptoms in Dementia, Exeter, UK.
ORCID: 0000-0001-6490-6037

Janet C Harwood (JC)

Division of Psychological Medicine and Clinical Neuroscience, School of Medicine, Cardiff University, Cardiff, UK.

Elise A Weamer (EA)

Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.

Lora McClain (L)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.

Rebecca Sims (R)

Division of Psychological Medicine and Clinical Neuroscience, School of Medicine, Cardiff University, Cardiff, UK.
ORCID: 0000-0002-3885-1199

Isabel Hernandez (I)

Research Center and Memory Clinic Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain.
CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.

Sonia Moreno-Grau (S)

Research Center and Memory Clinic Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain.
CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.

Lluís Tárraga (L)

Research Center and Memory Clinic Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain.
CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.

Mercè Boada (M)

Research Center and Memory Clinic Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain.
CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.
ORCID: 0000-0003-2617-3009

Emilio Alarcón-Martín (E)

Research Center and Memory Clinic Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain.

Sergi Valero (S)

Research Center and Memory Clinic Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain.
CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.

Yushi Liu (Y)

Global Statistical Science, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
ORCID: 0000-0003-4185-4187

Basavaraj Hooli (B)

Neurodegeneration Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
ORCID: 0000-0002-5461-1507

Dag Aarsland (D)

Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London and Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.

Geir Selbaek (G)

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

Sverre Bergh (S)

Research Centre of Age-related Functional Decline and Disease, Innlandet Hospital Trust, Pb 68, Ottestad, Norway.
ORCID: 0000-0001-9593-2967

Arvid Rongve (A)

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

Ingvild Saltvedt (I)

Geriatric Department, St. Olav Hospital, University Hospital of Trondheim, Trondheim, Norway.
Department of Neuromedicine and Movement science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
ORCID: 0000-0002-7897-9808

Håvard K Skjellegrind (HK)

HUNT Research Centre, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Levanger, Norway.
Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway.
ORCID: 0000-0003-3067-0016

Bo Engdahl (B)

Norwegian Institute of Public Health, Oslo, Norway.
ORCID: 0000-0002-9166-5782

Eystein Stordal (E)

Department of Mental Health, Norwegian University of Science and Technology, Trondheim, Norway.
ORCID: 0000-0002-2443-7923

Ole A Andreassen (OA)

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

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

Lavinia Athanasiu (L)

NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
ORCID: 0000-0002-3321-6997

Davide Seripa (D)

Department of Hematology and Stem Cell Transplant, Vito Fazzi Hospital, Lecce, Italy.

Barbara Borroni (B)

Centre for Neurodegenerative Disorders, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
ORCID: 0000-0001-9340-9814

Diego Albani (D)

Neuroscience Department, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
ORCID: 0000-0002-7050-6723

Gianluigi Forloni (G)

Neuroscience Department, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Patrizia Mecocci (P)

Institute of Gerontology and Geriatrics, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.

Alessandro Serretti (A)

Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy.
ORCID: 0000-0003-4363-3759

Diana De Ronchi (D)

Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy.

Antonis Politis (A)

1st Department of Psychiatry, Eginition Hospital, Medical School, National & Kapodistrian University of Athens, Athens, Greece.
ORCID: 0000-0003-0261-7517

Julie Williams (J)

Division of Psychological Medicine and Clinical Neuroscience, School of Medicine, Cardiff University, Cardiff, UK.
UK Dementia Research Institute @ Cardiff, School of Medicine, Cardiff University, Cardiff, UK.
ORCID: 0000-0002-4069-0259

Richard Mayeux (R)

Departments of Neurology, Psychiatry and Epidemiology, Columbia University, New York, NY, USA.

Tatiana Foroud (T)

Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
ORCID: 0000-0002-5549-2212

Agustin Ruiz (A)

Research Center and Memory Clinic Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain.
CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.
ORCID: 0000-0003-2633-2495

Clive Ballard (C)

University of Exeter Medical School, Exeter, UK.
ORCID: 0000-0003-0022-5632

Peter Holmans (P)

MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
ORCID: 0000-0003-0870-9412

Oscar L Lopez (OL)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
ORCID: 0000-0002-8546-8256

M Ilyas Kamboh (MI)

Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA.

Bernie Devlin (B)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
ORCID: 0000-0003-2524-4290

Robert A Sweet (RA)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA. sweetra@upmc.edu.
Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA. sweetra@upmc.edu.
ORCID: 0000-0001-9154-9709

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Classifications MeSH

questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie d'Alzheimer › Genome-wide association identifies the first...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Genome-wide association identifies the first...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Genome-wide association identifies the first...
questionsmedicales.fr › Comportement et mécanismes comportementaux › Manifestations neurocomportementales › Troubles de la perception › Hallucinations › Genome-wide association identifies the first...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Genome-wide association identifies the first...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Oxidoreductases › Oxidoreductases acting on sulfur group donors › Genome-wide association identifies the first...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Genome-wide association identifies the first...
questionsmedicales.fr › Troubles mentaux › Schizophrénie et troubles avec traits psychotiques › Troubles psychotiques › Genome-wide association identifies the first...
questionsmedicales.fr › Troubles mentaux › Schizophrénie et troubles avec traits psychotiques › Schizophrénie › Genome-wide association identifies the first...