Multi-tissue epigenetic analysis identifies distinct associations underlying insulin resistance and Alzheimer's disease at CPT1A locus.

Humans Alzheimer Disease / genetics Diabetes Mellitus, Type 2 / genetics DNA Methylation Epigenesis, Genetic Genetic Markers Genome-Wide Association Study / methods Insulin Resistance / genetics
Alzheimer’s disease DNA methylation Epigenetics FHS Insulin resistance ROSMAP

Journal

Clinical epigenetics
ISSN: 1868-7083
Titre abrégé: Clin Epigenetics
Pays: Germany
ID NLM: 101516977

Informations de publication

Date de publication:
27 10 2023
Historique:
received: 17 07 2023
accepted: 20 10 2023
medline: 30 10 2023
pubmed: 28 10 2023
entrez: 27 10 2023
Statut: epublish

Résumé

Insulin resistance (IR) is a major risk factor for Alzheimer's disease (AD) dementia. The mechanisms by which IR predisposes to AD are not well-understood. Epigenetic studies may help identify molecular signatures of IR associated with AD, thus improving our understanding of the biological and regulatory mechanisms linking IR and AD. We conducted an epigenome-wide association study of IR, quantified using the homeostatic model assessment of IR (HOMA-IR) and adjusted for body mass index, in 3,167 participants from the Framingham Heart Study (FHS) without type 2 diabetes at the time of blood draw used for methylation measurement. We identified DNA methylation markers associated with IR at the genome-wide level accounting for multiple testing (P < 1.1 × 10 We confirmed the strong association of blood DNA methylation with IR at three loci (cg17901584-DHCR24, cg17058475-CPT1A, cg00574958-CPT1A, and cg06500161-ABCG1). In FHS, higher levels of blood DNA methylation at cg00574958 and cg17058475 were both associated with lower IR (P = 2.4 × 10 Our results suggest potentially distinct epigenetic regulatory mechanisms between peripheral blood and dorsolateral prefrontal cortex tissues underlying IR and AD at CPT1A locus.

Sections du résumé

BACKGROUND
Insulin resistance (IR) is a major risk factor for Alzheimer's disease (AD) dementia. The mechanisms by which IR predisposes to AD are not well-understood. Epigenetic studies may help identify molecular signatures of IR associated with AD, thus improving our understanding of the biological and regulatory mechanisms linking IR and AD.
METHODS
We conducted an epigenome-wide association study of IR, quantified using the homeostatic model assessment of IR (HOMA-IR) and adjusted for body mass index, in 3,167 participants from the Framingham Heart Study (FHS) without type 2 diabetes at the time of blood draw used for methylation measurement. We identified DNA methylation markers associated with IR at the genome-wide level accounting for multiple testing (P < 1.1 × 10
RESULTS
We confirmed the strong association of blood DNA methylation with IR at three loci (cg17901584-DHCR24, cg17058475-CPT1A, cg00574958-CPT1A, and cg06500161-ABCG1). In FHS, higher levels of blood DNA methylation at cg00574958 and cg17058475 were both associated with lower IR (P = 2.4 × 10
CONCLUSIONS
Our results suggest potentially distinct epigenetic regulatory mechanisms between peripheral blood and dorsolateral prefrontal cortex tissues underlying IR and AD at CPT1A locus.

Identifiants

DOI: 10.1186/s13148-023-01589-4 PMID: 37891690 PMC: PMC10612362
pubmed: 37891690
doi: 10.1186/s13148-023-01589-4
pii: 10.1186/s13148-023-01589-4
pmc: PMC10612362
doi:

Substances chimiques

Genetic Markers 0
CPT1A protein, human EC 2.3.1.21

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

173

Subventions

Organisme : NIA NIH HHS
ID : R01 AG082360
Pays : United States
Organisme : NHLBI NIH HHS
ID : 75N92019D00031
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG049607
Pays : United States
Organisme : NIA NIH HHS
ID : K23 AG038444
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG054076
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG008122
Pays : United States
Organisme : NIA NIH HHS
ID : R00 AG066849
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL151855
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201500001I
Pays : United States
Organisme : NINDS NIH HHS
ID : UF1 NS125513
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG072972
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066546
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG068221
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG033040
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG059727
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG016495
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK078616
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC25195
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG033193
Pays : United States
Organisme : NHLBI NIH HHS
ID : K24 HL157960
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG031287
Pays : United States
Organisme : NIEHS NIH HHS
ID : R21 ES017950
Pays : United States

Informations de copyright

© 2023. The Author(s).

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Auteurs

Chloé Sarnowski (C)

Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA. Chloe.Sarnowski@uth.tmc.edu.

Tianxiao Huan (T)

Population Sciences Branch, National Heart, Lung and Blood Institutes of Health, Bethesda, MD, USA.

Yiyi Ma (Y)

Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA.

Roby Joehanes (R)

Population Sciences Branch, National Heart, Lung and Blood Institutes of Health, Bethesda, MD, USA.
The Framingham Heart Study, Framingham, MA, USA.

Alexa Beiser (A)

The Framingham Heart Study, Framingham, MA, USA.
Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA.
Department of Neurology, Boston University School of Medicine, Boston, MA, USA.

Charles S DeCarli (CS)

Department of Neurology, University of California, Davis, CA, USA.

Nancy L Heard-Costa (NL)

The Framingham Heart Study, Framingham, MA, USA.
Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA.

Daniel Levy (D)

Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
The Framingham Heart Study, Framingham, MA, USA.

Honghuang Lin (H)

Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.

Ching-Ti Liu (CT)

Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA.

Chunyu Liu (C)

Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA.

James B Meigs (JB)

Division of General Internal Medicine, Massachusetts General Hospital, Boston, MA, USA.
Department of Medicine, Harvard Medical School, Boston, MA, USA.
Programs in Metabolism and Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Claudia L Satizabal (CL)

The Framingham Heart Study, Framingham, MA, USA.
Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Department of Population Health Sciences, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.

Jose C Florez (JC)

Department of Medicine, Harvard Medical School, Boston, MA, USA.
Programs in Metabolism and Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Center for Genomic Medicine and Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA.

Marie-France Hivert (MF)

Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Harvard University, Boston, MA, USA.
Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA.
Department of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada.

Josée Dupuis (J)

Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA.
Department of Epidemiology, Biostatistics and Occupational Health, School of Population and Global Health, McGill University, Montreal, Canada.

Philip L De Jager (PL)

Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, NY, USA.

David A Bennett (DA)

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.

Sudha Seshadri (S)

The Framingham Heart Study, Framingham, MA, USA.
Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.

Alanna C Morrison (AC)

Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Multi-tissue epigenetic analysis identifies...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie d'Alzheimer › Multi-tissue epigenetic analysis identifies...
questionsmedicales.fr › Maladies endocriniennes › Diabète › Diabète de type 2 › Multi-tissue epigenetic analysis identifies...
questionsmedicales.fr › Phénomènes génétiques › Méthylation de l'ADN › Multi-tissue epigenetic analysis identifies...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Multi-tissue epigenetic analysis identifies...
questionsmedicales.fr › Phénomènes génétiques › Phénotype › Marqueurs génétiques › Multi-tissue epigenetic analysis identifies...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Multi-tissue epigenetic analysis identifies...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Résistance aux substances › Insulinorésistance › Multi-tissue epigenetic analysis identifies...