Transethnic meta-analysis of rare coding variants in PLCG2, ABI3, and TREM2 supports their general contribution to Alzheimer’s disease View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-01-31

AUTHORS

Maria Carolina Dalmasso, Luis Ignacio Brusco, Natividad Olivar, Carolina Muchnik, Claudia Hanses, Esther Milz, Julian Becker, Stefanie Heilmann-Heimbach, Per Hoffmann, Federico A. Prestia, Pablo Galeano, Mariana Soledad Sanchez Avalos, Luis Eduardo Martinez, Mariana Estela Carulla, Pablo Javier Azurmendi, Cynthia Liberczuk, Cristina Fezza, Marcelo Sampaño, Maria Fierens, Guillermo Jemar, Patricia Solis, Nancy Medel, Julieta Lisso, Zulma Sevillano, Paolo Bosco, Paola Bossù, Gianfranco Spalletta, Daniela Galimberti, Michelangelo Mancuso, Benedetta Nacmias, Sandro Sorbi, Patrizia Mecocci, Alberto Pilotto, Paolo Caffarra, Francesco Panza, Maria Bullido, Jordi Clarimon, Pascual Sánchez-Juan, Eliecer Coto, Florentino Sanchez-Garcia, Caroline Graff, Martin Ingelsson, Céline Bellenguez, Eduardo Miguel Castaño, Claudia Kairiyama, Daniel Gustavo Politis, Silvia Kochen, Horacio Scaro, Wolfgang Maier, Frank Jessen, Carlos Alberto Mangone, Jean-Charles Lambert, Laura Morelli, Alfredo Ramirez

ABSTRACT

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. More... »

PAGES

55

Journal

TITLE

Translational Psychiatry

ISSUE

1

VOLUME

9

Author Affiliations

  • Laboratory of Amyloidosis and Neurodegeneration, Fundación Instituto Leloir-IIBBA-CONICET, Ciudad Autónoma de Buenos Aires (C.A.B.A.), Buenos Aires, Argentina
  • Hospital Interzonal General de Agudos Eva Perón, San Martín, Buenos Aires, Argentina
  • Departamento Ciencias Fisiológicas UAII, Facultad de Medicina, UBA, C.A.B.A, Buenos Aires, Argentina
  • Laboratorio de Bioquímica Molecular, Facultad de Medicina, Instituto de Investigaciones Médicas A. Lanari, UBA, C.A.B.A, Buenos Aires, Argentina
  • Department of Psychiatry and Psychotherapy, University of Bonn, 53127 Bonn, Germany
  • Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University of Cologne, 50937 Cologne, 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
  • Ministerio de Salud de la Provincia de Jujuy, Programa del Adulto Mayor, San Salvador de Jujuy, Jujuy, Argentina
  • Centro de Neuropsiquiatría y Neurología de la Conducta (CENECON), Facultad de Medicina, Universidad de Buenos Aires (UBA), C.A.B.A, Buenos Aires, Argentina
  • Neurosciences and Complex Systems Unit (EnyS), CONICET, Hospital El Cruce “Dr. Néstor Kirchner”, Univ Arturo Jauretche, F. Varela, Buenos Aires, Argentina
  • Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Associazione Oasi Maria Santissima Srl, Troina, Italy
  • Department of Clinical and Behavioural Neurology, Experimental Neuropsychobiology Laboratory, Rome, Italy
  • Department of Clinical and Behavioural Neurology, Neuropsychiatry Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy
  • Neurodegenerative Diseases Center, University of Milan, Centro Dino Ferrari, Fondazione Ca′ Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy
  • Department of Experimental and Clinical Medicine, Neurological Institute, University of Pisa, Pisa, Italy
  • NEUROFARBA (Department of Neuroscience, Psychology, Drug Research and Child Health), University of Florence, Florence, Italy
  • IRCCS ′Don Carlo Gnocchi′, Florence, Italy
  • Section of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy
  • Geriatric Unit and Gerontology-Geriatrics Research Laboratory, Department of Medical Sciences, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
  • Alzheimer Center, FERB, Gazzaniga, Bergamo, Italy
  • Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari, Italy
  • Centro de Biología Molecular Severo Ochoa (CSIC-UAM), 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
  • Neurology Service and CIBERNED, ′Marqués de Valdecilla′ University Hospital (University of Cantabria and IDIVAL), Santander, Spain
  • Molecular Genetics Laboratory-Hospital, University of Central Asturias, Oviedo, Spain
  • Immunology Service, Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain
  • Division of Neurogeriatrics, Department NVS, Karolinska Institutet, Bioclincum J10:20, Solna, Sweden
  • Department of Public Health/Geriatrics, Uppsala University, Uppsala, Sweden
  • University Lille, U1167-Excellence Laboratory LabEx DISTALZ, F-59000 Lille, France
  • Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn, 53127 Bonn, Germany
  • Department of Psychiatry and Psychotherapy, University of Cologne, 50937 Cologne, Germany
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41398-019-0394-9

    DOI

    http://dx.doi.org/10.1038/s41398-019-0394-9

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1111774604

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30705288


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