Synonymous variants associated with Alzheimer disease in multiplex families.

Journal

Neurology. Genetics
ISSN: 2376-7839
Titre abrégé: Neurol Genet
Pays: United States
ID NLM: 101671068

Informations de publication

Date de publication:
Aug 2020
Historique:
received: 22 11 2019
accepted: 05 05 2020
entrez: 9 7 2020
pubmed: 9 7 2020
medline: 9 7 2020
Statut: epublish

Résumé

Synonymous variants can lead to disease; nevertheless, the majority of sequencing studies conducted in Alzheimer disease (AD) only assessed coding variation. To detect synonymous variants modulating AD risk, we conducted a whole-genome sequencing study on 67 Caribbean Hispanic (CH) families multiply affected by AD. Identified disease-associated variants were further assessed in an independent cohort of CHs, expression quantitative trait locus (eQTL) data, brain autopsy data, and functional experiments. Rare synonymous variants in 4 genes ( These findings suggest that

Identifiants

DOI: 10.1212/NXG.0000000000000450 PMID: 32637632 PMC: PMC7323483
pubmed: 32637632
doi: 10.1212/NXG.0000000000000450
pii: NG2019012393
pmc: PMC7323483
doi:

Types de publication

Journal Article

Langues

eng

Pagination

e450

Subventions

Organisme : NIA NIH HHS
ID : R01 AG067501
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG017917
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG010161
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG015473
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG015819
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG008702
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS095922
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG063908
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066462
Pays : United States

Informations de copyright

Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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Auteurs

Min Tang (M)

The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (M.E.A., B.V., R.L., P.L.J., R.M., I.S.-M., C.R.); The Gertrude H. Sergievsky Center (M.T., D.R.-D., R.L., R.M., C.R.); Department of Neurology (P.L.J., R.M., C.R.); Department of Epidemiology (R.M., C.R.); Department of Psychiatry (R.M.), Columbia University, New York; Department of Pathology and Cell Biology (M.E.A., I.S.-M.), Columbia University, New York; Rush Alzheimer's Disease Center (D.A.B.); Department of Neurological Sciences (D.A.B.); Department of Pathology (D.A.B.), Rush University Medical Center, Chicago, IL; Center for Innovation in Brain Science , Departments of Pharmacology and Neurology , University of Arizona College of Medicine (M.T.), Tucson; Department of Medicine (R.L.), College of Physicians and Surgeons, Columbia University, New York, NY; School of Medicine (M.M.), Mother and Teacher Pontifical Catholic University, Santiago, Dominican Republic; and The Krembil Centre for Neuroinformatics (D.F.), Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Maria Eugenia Alaniz (ME)

The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (M.E.A., B.V., R.L., P.L.J., R.M., I.S.-M., C.R.); The Gertrude H. Sergievsky Center (M.T., D.R.-D., R.L., R.M., C.R.); Department of Neurology (P.L.J., R.M., C.R.); Department of Epidemiology (R.M., C.R.); Department of Psychiatry (R.M.), Columbia University, New York; Department of Pathology and Cell Biology (M.E.A., I.S.-M.), Columbia University, New York; Rush Alzheimer's Disease Center (D.A.B.); Department of Neurological Sciences (D.A.B.); Department of Pathology (D.A.B.), Rush University Medical Center, Chicago, IL; Center for Innovation in Brain Science , Departments of Pharmacology and Neurology , University of Arizona College of Medicine (M.T.), Tucson; Department of Medicine (R.L.), College of Physicians and Surgeons, Columbia University, New York, NY; School of Medicine (M.M.), Mother and Teacher Pontifical Catholic University, Santiago, Dominican Republic; and The Krembil Centre for Neuroinformatics (D.F.), Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Daniel Felsky (D)

The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (M.E.A., B.V., R.L., P.L.J., R.M., I.S.-M., C.R.); The Gertrude H. Sergievsky Center (M.T., D.R.-D., R.L., R.M., C.R.); Department of Neurology (P.L.J., R.M., C.R.); Department of Epidemiology (R.M., C.R.); Department of Psychiatry (R.M.), Columbia University, New York; Department of Pathology and Cell Biology (M.E.A., I.S.-M.), Columbia University, New York; Rush Alzheimer's Disease Center (D.A.B.); Department of Neurological Sciences (D.A.B.); Department of Pathology (D.A.B.), Rush University Medical Center, Chicago, IL; Center for Innovation in Brain Science , Departments of Pharmacology and Neurology , University of Arizona College of Medicine (M.T.), Tucson; Department of Medicine (R.L.), College of Physicians and Surgeons, Columbia University, New York, NY; School of Medicine (M.M.), Mother and Teacher Pontifical Catholic University, Santiago, Dominican Republic; and The Krembil Centre for Neuroinformatics (D.F.), Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Badri Vardarajan (B)

The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (M.E.A., B.V., R.L., P.L.J., R.M., I.S.-M., C.R.); The Gertrude H. Sergievsky Center (M.T., D.R.-D., R.L., R.M., C.R.); Department of Neurology (P.L.J., R.M., C.R.); Department of Epidemiology (R.M., C.R.); Department of Psychiatry (R.M.), Columbia University, New York; Department of Pathology and Cell Biology (M.E.A., I.S.-M.), Columbia University, New York; Rush Alzheimer's Disease Center (D.A.B.); Department of Neurological Sciences (D.A.B.); Department of Pathology (D.A.B.), Rush University Medical Center, Chicago, IL; Center for Innovation in Brain Science , Departments of Pharmacology and Neurology , University of Arizona College of Medicine (M.T.), Tucson; Department of Medicine (R.L.), College of Physicians and Surgeons, Columbia University, New York, NY; School of Medicine (M.M.), Mother and Teacher Pontifical Catholic University, Santiago, Dominican Republic; and The Krembil Centre for Neuroinformatics (D.F.), Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Dolly Reyes-Dumeyer (D)

The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (M.E.A., B.V., R.L., P.L.J., R.M., I.S.-M., C.R.); The Gertrude H. Sergievsky Center (M.T., D.R.-D., R.L., R.M., C.R.); Department of Neurology (P.L.J., R.M., C.R.); Department of Epidemiology (R.M., C.R.); Department of Psychiatry (R.M.), Columbia University, New York; Department of Pathology and Cell Biology (M.E.A., I.S.-M.), Columbia University, New York; Rush Alzheimer's Disease Center (D.A.B.); Department of Neurological Sciences (D.A.B.); Department of Pathology (D.A.B.), Rush University Medical Center, Chicago, IL; Center for Innovation in Brain Science , Departments of Pharmacology and Neurology , University of Arizona College of Medicine (M.T.), Tucson; Department of Medicine (R.L.), College of Physicians and Surgeons, Columbia University, New York, NY; School of Medicine (M.M.), Mother and Teacher Pontifical Catholic University, Santiago, Dominican Republic; and The Krembil Centre for Neuroinformatics (D.F.), Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Rafael Lantigua (R)

The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (M.E.A., B.V., R.L., P.L.J., R.M., I.S.-M., C.R.); The Gertrude H. Sergievsky Center (M.T., D.R.-D., R.L., R.M., C.R.); Department of Neurology (P.L.J., R.M., C.R.); Department of Epidemiology (R.M., C.R.); Department of Psychiatry (R.M.), Columbia University, New York; Department of Pathology and Cell Biology (M.E.A., I.S.-M.), Columbia University, New York; Rush Alzheimer's Disease Center (D.A.B.); Department of Neurological Sciences (D.A.B.); Department of Pathology (D.A.B.), Rush University Medical Center, Chicago, IL; Center for Innovation in Brain Science , Departments of Pharmacology and Neurology , University of Arizona College of Medicine (M.T.), Tucson; Department of Medicine (R.L.), College of Physicians and Surgeons, Columbia University, New York, NY; School of Medicine (M.M.), Mother and Teacher Pontifical Catholic University, Santiago, Dominican Republic; and The Krembil Centre for Neuroinformatics (D.F.), Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Martin Medrano (M)

The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (M.E.A., B.V., R.L., P.L.J., R.M., I.S.-M., C.R.); The Gertrude H. Sergievsky Center (M.T., D.R.-D., R.L., R.M., C.R.); Department of Neurology (P.L.J., R.M., C.R.); Department of Epidemiology (R.M., C.R.); Department of Psychiatry (R.M.), Columbia University, New York; Department of Pathology and Cell Biology (M.E.A., I.S.-M.), Columbia University, New York; Rush Alzheimer's Disease Center (D.A.B.); Department of Neurological Sciences (D.A.B.); Department of Pathology (D.A.B.), Rush University Medical Center, Chicago, IL; Center for Innovation in Brain Science , Departments of Pharmacology and Neurology , University of Arizona College of Medicine (M.T.), Tucson; Department of Medicine (R.L.), College of Physicians and Surgeons, Columbia University, New York, NY; School of Medicine (M.M.), Mother and Teacher Pontifical Catholic University, Santiago, Dominican Republic; and The Krembil Centre for Neuroinformatics (D.F.), Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

David A Bennett (DA)

The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (M.E.A., B.V., R.L., P.L.J., R.M., I.S.-M., C.R.); The Gertrude H. Sergievsky Center (M.T., D.R.-D., R.L., R.M., C.R.); Department of Neurology (P.L.J., R.M., C.R.); Department of Epidemiology (R.M., C.R.); Department of Psychiatry (R.M.), Columbia University, New York; Department of Pathology and Cell Biology (M.E.A., I.S.-M.), Columbia University, New York; Rush Alzheimer's Disease Center (D.A.B.); Department of Neurological Sciences (D.A.B.); Department of Pathology (D.A.B.), Rush University Medical Center, Chicago, IL; Center for Innovation in Brain Science , Departments of Pharmacology and Neurology , University of Arizona College of Medicine (M.T.), Tucson; Department of Medicine (R.L.), College of Physicians and Surgeons, Columbia University, New York, NY; School of Medicine (M.M.), Mother and Teacher Pontifical Catholic University, Santiago, Dominican Republic; and The Krembil Centre for Neuroinformatics (D.F.), Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Philip L de Jager (PL)

The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (M.E.A., B.V., R.L., P.L.J., R.M., I.S.-M., C.R.); The Gertrude H. Sergievsky Center (M.T., D.R.-D., R.L., R.M., C.R.); Department of Neurology (P.L.J., R.M., C.R.); Department of Epidemiology (R.M., C.R.); Department of Psychiatry (R.M.), Columbia University, New York; Department of Pathology and Cell Biology (M.E.A., I.S.-M.), Columbia University, New York; Rush Alzheimer's Disease Center (D.A.B.); Department of Neurological Sciences (D.A.B.); Department of Pathology (D.A.B.), Rush University Medical Center, Chicago, IL; Center for Innovation in Brain Science , Departments of Pharmacology and Neurology , University of Arizona College of Medicine (M.T.), Tucson; Department of Medicine (R.L.), College of Physicians and Surgeons, Columbia University, New York, NY; School of Medicine (M.M.), Mother and Teacher Pontifical Catholic University, Santiago, Dominican Republic; and The Krembil Centre for Neuroinformatics (D.F.), Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Richard Mayeux (R)

The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (M.E.A., B.V., R.L., P.L.J., R.M., I.S.-M., C.R.); The Gertrude H. Sergievsky Center (M.T., D.R.-D., R.L., R.M., C.R.); Department of Neurology (P.L.J., R.M., C.R.); Department of Epidemiology (R.M., C.R.); Department of Psychiatry (R.M.), Columbia University, New York; Department of Pathology and Cell Biology (M.E.A., I.S.-M.), Columbia University, New York; Rush Alzheimer's Disease Center (D.A.B.); Department of Neurological Sciences (D.A.B.); Department of Pathology (D.A.B.), Rush University Medical Center, Chicago, IL; Center for Innovation in Brain Science , Departments of Pharmacology and Neurology , University of Arizona College of Medicine (M.T.), Tucson; Department of Medicine (R.L.), College of Physicians and Surgeons, Columbia University, New York, NY; School of Medicine (M.M.), Mother and Teacher Pontifical Catholic University, Santiago, Dominican Republic; and The Krembil Centre for Neuroinformatics (D.F.), Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Ismael Santa-Maria (I)

The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (M.E.A., B.V., R.L., P.L.J., R.M., I.S.-M., C.R.); The Gertrude H. Sergievsky Center (M.T., D.R.-D., R.L., R.M., C.R.); Department of Neurology (P.L.J., R.M., C.R.); Department of Epidemiology (R.M., C.R.); Department of Psychiatry (R.M.), Columbia University, New York; Department of Pathology and Cell Biology (M.E.A., I.S.-M.), Columbia University, New York; Rush Alzheimer's Disease Center (D.A.B.); Department of Neurological Sciences (D.A.B.); Department of Pathology (D.A.B.), Rush University Medical Center, Chicago, IL; Center for Innovation in Brain Science , Departments of Pharmacology and Neurology , University of Arizona College of Medicine (M.T.), Tucson; Department of Medicine (R.L.), College of Physicians and Surgeons, Columbia University, New York, NY; School of Medicine (M.M.), Mother and Teacher Pontifical Catholic University, Santiago, Dominican Republic; and The Krembil Centre for Neuroinformatics (D.F.), Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Christiane Reitz (C)

The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (M.E.A., B.V., R.L., P.L.J., R.M., I.S.-M., C.R.); The Gertrude H. Sergievsky Center (M.T., D.R.-D., R.L., R.M., C.R.); Department of Neurology (P.L.J., R.M., C.R.); Department of Epidemiology (R.M., C.R.); Department of Psychiatry (R.M.), Columbia University, New York; Department of Pathology and Cell Biology (M.E.A., I.S.-M.), Columbia University, New York; Rush Alzheimer's Disease Center (D.A.B.); Department of Neurological Sciences (D.A.B.); Department of Pathology (D.A.B.), Rush University Medical Center, Chicago, IL; Center for Innovation in Brain Science , Departments of Pharmacology and Neurology , University of Arizona College of Medicine (M.T.), Tucson; Department of Medicine (R.L.), College of Physicians and Surgeons, Columbia University, New York, NY; School of Medicine (M.M.), Mother and Teacher Pontifical Catholic University, Santiago, Dominican Republic; and The Krembil Centre for Neuroinformatics (D.F.), Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Classifications MeSH