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Transl Psychiatry. 2019 Jan 31;9(1):55. doi: 10.1038/s41398-019-0394-9.

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

Author information

1
Laboratory of Amyloidosis and Neurodegeneration, Fundación Instituto Leloir-IIBBA-CONICET, Ciudad Autónoma de Buenos Aires (C.A.B.A.), Buenos Aires, Argentina.
2
Centro de Neuropsiquiatría y Neurología de la Conducta (CENECON), Facultad de Medicina, Universidad de Buenos Aires (UBA), C.A.B.A, Buenos Aires, Argentina.
3
Departamento Ciencias Fisiológicas UAII, Facultad de Medicina, UBA, C.A.B.A, Buenos Aires, Argentina.
4
Hospital Interzonal General de Agudos Eva Perón, San Martín, Buenos Aires, Argentina.
5
Laboratorio de Bioquímica Molecular, Facultad de Medicina, Instituto de Investigaciones Médicas A. Lanari, UBA, C.A.B.A, Buenos Aires, Argentina.
6
Department of Psychiatry and Psychotherapy, University of Bonn, 53127, Bonn, Germany.
7
Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University of Cologne, 50937, Cologne, Germany.
8
Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital, 53127, Bonn, Germany.
9
Department of Genomics, Life & Brain Center, University of Bonn, 53127, Bonn, Germany.
10
Division of Medical Genetics, University Hospital and Department of Biomedicine, University of Basel, CH-4058, Basel, Switzerland.
11
Ministerio de Salud de la Provincia de Jujuy, Programa del Adulto Mayor, San Salvador de Jujuy, Jujuy, Argentina.
12
Neurosciences and Complex Systems Unit (EnyS), CONICET, Hospital El Cruce "Dr. Néstor Kirchner", Univ Arturo Jauretche, F. Varela, Buenos Aires, Argentina.
13
Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Associazione Oasi Maria Santissima Srl, Troina, Italy.
14
Department of Clinical and Behavioural Neurology, Experimental Neuropsychobiology Laboratory, Rome, Italy.
15
Department of Clinical and Behavioural Neurology, Neuropsychiatry Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.
16
Neurodegenerative Diseases Center, University of Milan, Centro Dino Ferrari, Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
17
Department of Experimental and Clinical Medicine, Neurological Institute, University of Pisa, Pisa, Italy.
18
NEUROFARBA (Department of Neuroscience, Psychology, Drug Research and Child Health), University of Florence, Florence, Italy.
19
IRCCS 'Don Carlo Gnocchi', Florence, Italy.
20
Section of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy.
21
Geriatric Unit and Gerontology-Geriatrics Research Laboratory, Department of Medical Sciences, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
22
Section of Neuroscience, DIMEC, University of Parma, Parma, Italy.
23
Alzheimer Center, FERB, Gazzaniga, Bergamo, Italy.
24
Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari, Italy.
25
Instituto de Investigación Sanitaria Hospital la Paz (IdiPAZ), Madrid, Spain.
26
Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
27
Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain.
28
Memory Unit, Neurology Department and Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain.
29
Neurology Service and CIBERNED, 'Marqués de Valdecilla' University Hospital (University of Cantabria and IDIVAL), Santander, Spain.
30
Molecular Genetics Laboratory-Hospital, University of Central Asturias, Oviedo, Spain.
31
Immunology Service, Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain.
32
Genetics Unit, Theme Aging, Karolinska University Hospital, Solna, Sweden.
33
Division of Neurogeriatrics, Department NVS, Karolinska Institutet, Bioclincum J10:20, Solna, Sweden.
34
Department of Public Health/Geriatrics, Uppsala University, Uppsala, Sweden.
35
INSERM, U1167, RID-AGE-Risk Factors and Molecular Determinants of Aging-Related Diseases, F-59000, Lille, France.
36
Institut Pasteur de Lille, F-59000, Lille, France.
37
University Lille, U1167-Excellence Laboratory LabEx DISTALZ, F-59000, Lille, France.
38
German Center for Neurodegenerative Diseases (DZNE), 53127, Bonn, Germany.
39
Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn, 53127, Bonn, Germany.
40
Department of Psychiatry and Psychotherapy, University of Cologne, 50937, Cologne, Germany.
41
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.
42
Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University of Cologne, 50937, Cologne, Germany. alfredo.ramirez@uk-koeln.de.
43
Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn, 53127, Bonn, Germany. alfredo.ramirez@uk-koeln.de.

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.

PMID:
30705288
PMCID:
PMC6355764
DOI:
10.1038/s41398-019-0394-9
[Indexed for MEDLINE]
Free PMC Article

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