Epigenetic and genetic risk of Alzheimer disease from autopsied brains in two ethnic groups.

Humans Alzheimer Disease / genetics Female Male Epigenesis, Genetic Aged White People / genetics Genetic Predisposition to Disease Brain / pathology Polymorphism, Single Nucleotide Hispanic or Latino / genetics Aged, 80 and over Genome-Wide Association Study DNA Methylation Autopsy Caribbean Region / ethnology
Alzheimer’s disease CpG-related single nucleotide polymorphism Epigenetics Genetics Hispanics Non-Hispanic Whites

Journal

Acta neuropathologica
ISSN: 1432-0533
Titre abrégé: Acta Neuropathol
Pays: Germany
ID NLM: 0412041

Informations de publication

Date de publication:
23 Aug 2024
Historique:
received: 24 03 2024
accepted: 01 08 2024
revised: 01 08 2024
medline: 23 8 2024
pubmed: 23 8 2024
entrez: 23 8 2024
Statut: epublish

Résumé

Genetic variants and epigenetic features both contribute to the risk of Alzheimer's disease (AD). We studied the AD association of CpG-related single nucleotide polymorphisms (CGS), which act as a hub of both the genetic and epigenetic effects, in Caribbean Hispanics (CH) and generalized the findings to Non-Hispanic Whites (NHW). First, we conducted a genome-wide, sliding-window-based association with AD, in 7,155 CH and 1,283 NHW participants. Next, using data from the dorsolateral prefrontal cortex in 179 CH brains, we tested the cis- and trans-effects of AD-associated CGS on brain DNA methylation to mRNA expression. For the genes with significant cis- and trans-effects, we investigated their enriched pathways. We identified six genetic loci in CH with CGS dosage associated with AD at genome-wide significance levels: ADAM20 (Score = 55.19, P = 4.06 × 10

Identifiants

DOI: 10.1007/s00401-024-02778-y PMID: 39177846
pubmed: 39177846
doi: 10.1007/s00401-024-02778-y
pii: 10.1007/s00401-024-02778-y
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

27

Subventions

Organisme : NIA NIH HHS
ID : R01 AG072474
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG066107
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG067501
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG062517
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG072972
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG062429
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG062677
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG003949
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG072979
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG066597
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG062418
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1TR001873
Pays : United States
Organisme : Florida Department of Health, Ed and Ethel Moore Alzheimer Disease Research Program
ID : 20A22
Organisme : Florida Department of Health, Ed and Ethel Moore Alzheimer Disease Research Program
ID : 8AZ06

Informations de copyright

© 2024. The Author(s).

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Auteurs

Yiyi Ma (Y)

Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
G.H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, The New York Presbyterian Hospital, 630 West 168th street, New York, NY, 10032, USA.

Dolly Reyes-Dumeyer (D)

Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
G.H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, The New York Presbyterian Hospital, 630 West 168th street, New York, NY, 10032, USA.

Angel Piriz (A)

Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.

Patricia Recio (P)

CEDIMAT, Santo Domingo, Dominican Republic.

Diones Rivera Mejia (DR)

CEDIMAT, Santo Domingo, Dominican Republic.
Universidad Pedro Henríquez Urena, Santo Domingo, Dominican Republic.

Martin Medrano (M)

Pontíficia Universidad Católica Madre y Maestra (PUCMM), Santiago, Dominican Republic.

Rafael A Lantigua (RA)

Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, The New York Presbyterian Hospital, New York, NY, USA.

Jean Paul G Vonsattel (JPG)

Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.

Giuseppe Tosto (G)

Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
G.H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.

Andrew F Teich (AF)

Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, The New York Presbyterian Hospital, 630 West 168th street, New York, NY, 10032, USA.
Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.

Benjamin Ciener (B)

Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, The New York Presbyterian Hospital, 630 West 168th street, New York, NY, 10032, USA.
Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.

Sandra Leskinen (S)

Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, The New York Presbyterian Hospital, 630 West 168th street, New York, NY, 10032, USA.
Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.

Sharanya Sivakumar (S)

Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, The New York Presbyterian Hospital, 630 West 168th street, New York, NY, 10032, USA.
Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.

Michael DeTure (M)

Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA.

Duara Ranjan (D)

Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA.

Dennis Dickson (D)

Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA.

Melissa Murray (M)

Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA.

Edward Lee (E)

Department of Neurology and Penn Alzheimer's Disease Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

David A Wolk (DA)

Department of Neurology and Penn Alzheimer's Disease Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Lee-Way Jin (LW)

Department of Pathology and Laboratory Medicine, School of Medicine, University of California Davis, Sacramento, CA, 95817, USA.

Brittany N Dugger (BN)

Department of Pathology and Laboratory Medicine, School of Medicine, University of California Davis, Sacramento, CA, 95817, USA.

Annie Hiniker (A)

Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.

Robert A Rissman (RA)

Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.

Richard Mayeux (R)

Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA. rpm2@cumc.columbia.edu.
G.H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA. rpm2@cumc.columbia.edu.
Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, The New York Presbyterian Hospital, 630 West 168th street, New York, NY, 10032, USA. rpm2@cumc.columbia.edu.

Badri N Vardarajan (BN)

Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA. bnv2103@cumc.columbia.edu.
G.H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA. bnv2103@cumc.columbia.edu.
Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, The New York Presbyterian Hospital, 630 West 168th street, New York, NY, 10032, USA. bnv2103@cumc.columbia.edu.
ORCID: 0000-0002-5560-4085

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Epigenetic and genetic risk of Alzheimer...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie d'Alzheimer › Epigenetic and genetic risk of Alzheimer...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Epigenetic and genetic risk of Alzheimer...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Epigenetic and genetic risk of Alzheimer...
questionsmedicales.fr › Personnes › Blancs › Epigenetic and genetic risk of Alzheimer...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Epigenetic and genetic risk of Alzheimer...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Epigenetic and genetic risk of Alzheimer...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Epigenetic and genetic risk of Alzheimer...
questionsmedicales.fr › Personnes › Nord-Américains › Groupes de population aux États-Unis › Hispanique ou Latino › Epigenetic and genetic risk of Alzheimer...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Sujet âgé de 80 ans ou plus › Epigenetic and genetic risk of Alzheimer...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Epigenetic and genetic risk of Alzheimer...
questionsmedicales.fr › Phénomènes génétiques › Méthylation de l'ADN › Epigenetic and genetic risk of Alzheimer...
questionsmedicales.fr › Sciences sociales › Criminologie › Sciences légales › Médecine légale › Autopsie › Epigenetic and genetic risk of Alzheimer...
questionsmedicales.fr › Régions géographiques › Amériques › Caraïbe › Epigenetic and genetic risk of Alzheimer...