Transethnic meta-analysis of rare coding variants in PLCG2, ABI3, and TREM2 supports their general contribution to Alzheimer's disease.


Journal

Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664

Informations de publication

Date de publication:
31 01 2019
Historique:
received: 02 08 2018
accepted: 01 01 2019
revised: 26 11 2018
entrez: 2 2 2019
pubmed: 2 2 2019
medline: 14 6 2019
Statut: epublish

Résumé

Rare coding variants in TREM2, PLCG2, and ABI3 were recently associated with the susceptibility to Alzheimer's disease (AD) in Caucasians. Frequencies and AD-associated effects of variants differ across ethnicities. To start filling the gap on AD genetics in South America and assess the impact of these variants across ethnicity, we studied these variants in Argentinian population in association with ancestry. TREM2 (rs143332484 and rs75932628), PLCG2 (rs72824905), and ABI3 (rs616338) were genotyped in 419 AD cases and 486 controls. Meta-analysis with European population was performed. Ancestry was estimated from genome-wide genotyping results. All variants show similar frequencies and odds ratios to those previously reported. Their association with AD reach statistical significance by meta-analysis. Although the Argentinian population is an admixture, variant carriers presented mainly Caucasian ancestry. Rare coding variants in TREM2, PLCG2, and ABI3 also modulate susceptibility to AD in populations from Argentina, and they may have a European heritage.

Identifiants

pubmed: 30705288
doi: 10.1038/s41398-019-0394-9
pii: 10.1038/s41398-019-0394-9
pmc: PMC6355764
doi:

Substances chimiques

ABI3 protein, human 0
Adaptor Proteins, Signal Transducing 0
Membrane Glycoproteins 0
Receptors, Immunologic 0
TREM2 protein, human 0
Phospholipase C gamma EC 3.1.4.3

Types de publication

Journal Article Meta-Analysis Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

55

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Auteurs

Maria Carolina Dalmasso (MC)

Laboratory of Amyloidosis and Neurodegeneration, Fundación Instituto Leloir-IIBBA-CONICET, Ciudad Autónoma de Buenos Aires (C.A.B.A.), Buenos Aires, Argentina.

Luis Ignacio Brusco (LI)

Centro de Neuropsiquiatría y Neurología de la Conducta (CENECON), Facultad de Medicina, Universidad de Buenos Aires (UBA), C.A.B.A, Buenos Aires, Argentina.
Departamento Ciencias Fisiológicas UAII, Facultad de Medicina, UBA, C.A.B.A, Buenos Aires, Argentina.
Hospital Interzonal General de Agudos Eva Perón, San Martín, Buenos Aires, Argentina.

Natividad Olivar (N)

Centro de Neuropsiquiatría y Neurología de la Conducta (CENECON), Facultad de Medicina, Universidad de Buenos Aires (UBA), C.A.B.A, Buenos Aires, Argentina.
Departamento Ciencias Fisiológicas UAII, Facultad de Medicina, UBA, C.A.B.A, Buenos Aires, Argentina.

Carolina Muchnik (C)

Laboratorio de Bioquímica Molecular, Facultad de Medicina, Instituto de Investigaciones Médicas A. Lanari, UBA, C.A.B.A, Buenos Aires, Argentina.

Claudia Hanses (C)

Department of Psychiatry and Psychotherapy, University of Bonn, 53127, Bonn, Germany.

Esther Milz (E)

Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University of Cologne, 50937, Cologne, Germany.

Julian Becker (J)

Department of Psychiatry and Psychotherapy, University of Bonn, 53127, Bonn, Germany.

Stefanie Heilmann-Heimbach (S)

Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital, 53127, Bonn, Germany.
Department of Genomics, Life & Brain Center, University of Bonn, 53127, Bonn, Germany.

Per Hoffmann (P)

Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital, 53127, Bonn, Germany.
Department of Genomics, Life & Brain Center, University of Bonn, 53127, Bonn, Germany.
Division of Medical Genetics, University Hospital and Department of Biomedicine, University of Basel, CH-4058, Basel, Switzerland.

Federico A Prestia (FA)

Laboratory of Amyloidosis and Neurodegeneration, Fundación Instituto Leloir-IIBBA-CONICET, Ciudad Autónoma de Buenos Aires (C.A.B.A.), Buenos Aires, Argentina.

Pablo Galeano (P)

Laboratory of Amyloidosis and Neurodegeneration, Fundación Instituto Leloir-IIBBA-CONICET, Ciudad Autónoma de Buenos Aires (C.A.B.A.), Buenos Aires, Argentina.

Mariana Soledad Sanchez Avalos (MSS)

Ministerio de Salud de la Provincia de Jujuy, Programa del Adulto Mayor, San Salvador de Jujuy, Jujuy, Argentina.

Luis Eduardo Martinez (LE)

Hospital Interzonal General de Agudos Eva Perón, San Martín, Buenos Aires, Argentina.

Mariana Estela Carulla (ME)

Hospital Interzonal General de Agudos Eva Perón, San Martín, Buenos Aires, Argentina.

Pablo Javier Azurmendi (PJ)

Laboratorio de Bioquímica Molecular, Facultad de Medicina, Instituto de Investigaciones Médicas A. Lanari, UBA, C.A.B.A, Buenos Aires, Argentina.

Cynthia Liberczuk (C)

Centro de Neuropsiquiatría y Neurología de la Conducta (CENECON), Facultad de Medicina, Universidad de Buenos Aires (UBA), C.A.B.A, Buenos Aires, Argentina.

Cristina Fezza (C)

Laboratorio de Bioquímica Molecular, Facultad de Medicina, Instituto de Investigaciones Médicas A. Lanari, UBA, C.A.B.A, Buenos Aires, Argentina.

Marcelo Sampaño (M)

Centro de Neuropsiquiatría y Neurología de la Conducta (CENECON), Facultad de Medicina, Universidad de Buenos Aires (UBA), C.A.B.A, Buenos Aires, Argentina.

Maria Fierens (M)

Centro de Neuropsiquiatría y Neurología de la Conducta (CENECON), Facultad de Medicina, Universidad de Buenos Aires (UBA), C.A.B.A, Buenos Aires, Argentina.

Guillermo Jemar (G)

Centro de Neuropsiquiatría y Neurología de la Conducta (CENECON), Facultad de Medicina, Universidad de Buenos Aires (UBA), C.A.B.A, Buenos Aires, Argentina.

Patricia Solis (P)

Neurosciences and Complex Systems Unit (EnyS), CONICET, Hospital El Cruce "Dr. Néstor Kirchner", Univ Arturo Jauretche, F. Varela, Buenos Aires, Argentina.

Nancy Medel (N)

Neurosciences and Complex Systems Unit (EnyS), CONICET, Hospital El Cruce "Dr. Néstor Kirchner", Univ Arturo Jauretche, F. Varela, Buenos Aires, Argentina.

Julieta Lisso (J)

Neurosciences and Complex Systems Unit (EnyS), CONICET, Hospital El Cruce "Dr. Néstor Kirchner", Univ Arturo Jauretche, F. Varela, Buenos Aires, Argentina.

Zulma Sevillano (Z)

Neurosciences and Complex Systems Unit (EnyS), CONICET, Hospital El Cruce "Dr. Néstor Kirchner", Univ Arturo Jauretche, F. Varela, Buenos Aires, Argentina.

Paolo Bosco (P)

Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Associazione Oasi Maria Santissima Srl, Troina, Italy.

Paola Bossù (P)

Department of Clinical and Behavioural Neurology, Experimental Neuropsychobiology Laboratory, Rome, Italy.

Gianfranco Spalletta (G)

Department of Clinical and Behavioural Neurology, Neuropsychiatry Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.

Daniela Galimberti (D)

Neurodegenerative Diseases Center, University of Milan, Centro Dino Ferrari, Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.

Michelangelo Mancuso (M)

Department of Experimental and Clinical Medicine, Neurological Institute, University of Pisa, Pisa, Italy.

Benedetta Nacmias (B)

NEUROFARBA (Department of Neuroscience, Psychology, Drug Research and Child Health), University of Florence, Florence, Italy.

Sandro Sorbi (S)

NEUROFARBA (Department of Neuroscience, Psychology, Drug Research and Child Health), University of Florence, Florence, Italy.
IRCCS 'Don Carlo Gnocchi', Florence, Italy.

Patrizia Mecocci (P)

Section of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy.

Alberto Pilotto (A)

Geriatric Unit and Gerontology-Geriatrics Research Laboratory, Department of Medical Sciences, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.

Paolo Caffarra (P)

Section of Neuroscience, DIMEC, University of Parma, Parma, Italy.
Alzheimer Center, FERB, Gazzaniga, Bergamo, Italy.

Francesco Panza (F)

Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari, Italy.

Maria Bullido (M)

Instituto de Investigación Sanitaria Hospital la Paz (IdiPAZ), Madrid, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain.

Jordi Clarimon (J)

Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
Memory Unit, Neurology Department and Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain.

Pascual Sánchez-Juan (P)

Neurology Service and CIBERNED, 'Marqués de Valdecilla' University Hospital (University of Cantabria and IDIVAL), Santander, Spain.

Eliecer Coto (E)

Molecular Genetics Laboratory-Hospital, University of Central Asturias, Oviedo, Spain.

Florentino Sanchez-Garcia (F)

Immunology Service, Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain.

Caroline Graff (C)

Genetics Unit, Theme Aging, Karolinska University Hospital, Solna, Sweden.
Division of Neurogeriatrics, Department NVS, Karolinska Institutet, Bioclincum J10:20, Solna, Sweden.

Martin Ingelsson (M)

Department of Public Health/Geriatrics, Uppsala University, Uppsala, Sweden.

Céline Bellenguez (C)

INSERM, U1167, RID-AGE-Risk Factors and Molecular Determinants of Aging-Related Diseases, F-59000, Lille, France.
Institut Pasteur de Lille, F-59000, Lille, France.
University Lille, U1167-Excellence Laboratory LabEx DISTALZ, F-59000, Lille, France.

Eduardo Miguel Castaño (EM)

Laboratory of Amyloidosis and Neurodegeneration, Fundación Instituto Leloir-IIBBA-CONICET, Ciudad Autónoma de Buenos Aires (C.A.B.A.), Buenos Aires, Argentina.

Claudia Kairiyama (C)

Hospital Interzonal General de Agudos Eva Perón, San Martín, Buenos Aires, Argentina.

Daniel Gustavo Politis (DG)

Hospital Interzonal General de Agudos Eva Perón, San Martín, Buenos Aires, Argentina.

Silvia Kochen (S)

Neurosciences and Complex Systems Unit (EnyS), CONICET, Hospital El Cruce "Dr. Néstor Kirchner", Univ Arturo Jauretche, F. Varela, Buenos Aires, Argentina.

Horacio Scaro (H)

Ministerio de Salud de la Provincia de Jujuy, Programa del Adulto Mayor, San Salvador de Jujuy, Jujuy, Argentina.

Wolfgang Maier (W)

German Center for Neurodegenerative Diseases (DZNE), 53127, Bonn, Germany.
Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn, 53127, Bonn, Germany.

Frank Jessen (F)

German Center for Neurodegenerative Diseases (DZNE), 53127, Bonn, Germany.
Department of Psychiatry and Psychotherapy, University of Cologne, 50937, Cologne, Germany.

Carlos Alberto Mangone (CA)

Centro de Neuropsiquiatría y Neurología de la Conducta (CENECON), Facultad de Medicina, Universidad de Buenos Aires (UBA), C.A.B.A, Buenos Aires, Argentina.

Jean-Charles Lambert (JC)

INSERM, U1167, RID-AGE-Risk Factors and Molecular Determinants of Aging-Related Diseases, F-59000, Lille, France.
Institut Pasteur de Lille, F-59000, Lille, France.
University Lille, U1167-Excellence Laboratory LabEx DISTALZ, F-59000, Lille, France.

Laura Morelli (L)

Laboratory of Amyloidosis and Neurodegeneration, Fundación Instituto Leloir-IIBBA-CONICET, Ciudad Autónoma de Buenos Aires (C.A.B.A.), Buenos Aires, Argentina. lmorelli@leloir.org.ar.

Alfredo Ramirez (A)

Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University of Cologne, 50937, Cologne, Germany. alfredo.ramirez@uk-koeln.de.
Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn, 53127, Bonn, Germany. alfredo.ramirez@uk-koeln.de.

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Classifications MeSH