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.

Details

Title
Transethnic meta-analysis of rare coding variants in PLCG2, ABI3, and TREM2 supports their general contribution to Alzheimer’s disease
Author
Dalmasso, Maria Carolina 1 ; Brusco, Luis Ignacio 2 ; Olivar Natividad 3 ; Muchnik Carolina 4 ; Hanses, Claudia 5 ; Milz, Esther 6 ; Becker, Julian 5 ; Heilmann-Heimbach Stefanie 7 ; Hoffmann, Per 8   VIAFID ORCID Logo  ; Prestia, Federico A 9 ; Galeano Pablo 9   VIAFID ORCID Logo  ; Avalos Mariana Soledad Sanchez 10 ; Martinez, Luis Eduardo 11 ; Carulla, Mariana Estela 11 ; Azurmendi Pablo Javier 12   VIAFID ORCID Logo  ; Liberczuk Cynthia 13 ; Fezza Cristina 4 ; Sampaño Marcelo 13 ; Fierens, Maria 13 ; Jemar Guillermo 13 ; Solis, Patricia 14 ; Medel, Nancy 14 ; Lisso Julieta 14 ; Sevillano Zulma 14 ; Bosco, Paolo 15 ; Bossù Paola 16 ; Spalletta Gianfranco 17 ; Galimberti, Daniela 18 ; Mancuso Michelangelo 19 ; Nacmias Benedetta 20 ; Sorbi Sandro 21 ; Mecocci Patrizia 22 ; Pilotto Alberto 23 ; Caffarra Paolo 24 ; Panza, Francesco 25   VIAFID ORCID Logo  ; Bullido, Maria 26 ; Clarimon Jordi 27 ; Sánchez-Juan, Pascual 28 ; Coto Eliecer 29 ; Sanchez-Garcia, Florentino 30 ; Graff, Caroline 31 ; Ingelsson, Martin 32 ; Bellenguez Céline 33   VIAFID ORCID Logo  ; Castaño, Eduardo Miguel 34 ; Kairiyama Claudia 35 ; Politis, Daniel Gustavo 35 ; Kochen, Silvia 14 ; Scaro Horacio 36 ; Maier, Wolfgang 37 ; Jessen, Frank 38 ; Mangone, Carlos Alberto 13 ; Lambert, Jean-Charles 33   VIAFID ORCID Logo  ; Morelli, Laura 34 ; Ramirez, Alfredo 39   VIAFID ORCID Logo 

1  Ciudad Autónoma de Buenos Aires (C.A.B.A.), Laboratory of Amyloidosis and Neurodegeneration, Fundación Instituto Leloir-IIBBA-CONICET, Buenos Aires, Argentina 
2  Universidad de Buenos Aires (UBA), C.A.B.A, Centro de Neuropsiquiatría y Neurología de la Conducta (CENECON), Facultad de Medicina, Buenos Aires, Argentina (GRID:grid.7345.5) (ISNI:0000 0001 0056 1981); C.A.B.A, Departamento Ciencias Fisiológicas UAII, Facultad de Medicina, UBA, Buenos Aires, Argentina (GRID:grid.7345.5) (ISNI:0000 0001 0056 1981); Hospital Interzonal General de Agudos Eva Perón, Buenos Aires, Argentina (GRID:grid.7345.5) 
3  Universidad de Buenos Aires (UBA), C.A.B.A, Centro de Neuropsiquiatría y Neurología de la Conducta (CENECON), Facultad de Medicina, Buenos Aires, Argentina (GRID:grid.7345.5) (ISNI:0000 0001 0056 1981); C.A.B.A, Departamento Ciencias Fisiológicas UAII, Facultad de Medicina, UBA, Buenos Aires, Argentina (GRID:grid.7345.5) (ISNI:0000 0001 0056 1981) 
4  C.A.B.A, Laboratorio de Bioquímica Molecular, Facultad de Medicina, Instituto de Investigaciones Médicas A. Lanari, UBA, Buenos Aires, Argentina (GRID:grid.7345.5) 
5  University of Bonn, Department of Psychiatry and Psychotherapy, Bonn, Germany (GRID:grid.10388.32) (ISNI:0000 0001 2240 3300) 
6  University of Cologne, Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Cologne, Germany (GRID:grid.6190.e) (ISNI:0000 0000 8580 3777) 
7  School of Medicine & University Hospital, Institute of Human Genetics, University of Bonn, Bonn, Germany (GRID:grid.10388.32) (ISNI:0000 0001 2240 3300); University of Bonn, Department of Genomics, Life & Brain Center, Bonn, Germany (GRID:grid.10388.32) (ISNI:0000 0001 2240 3300) 
8  School of Medicine & University Hospital, Institute of Human Genetics, University of Bonn, Bonn, Germany (GRID:grid.10388.32) (ISNI:0000 0001 2240 3300); University of Bonn, Department of Genomics, Life & Brain Center, Bonn, Germany (GRID:grid.10388.32) (ISNI:0000 0001 2240 3300); University of Basel, Division of Medical Genetics, University Hospital and Department of Biomedicine, Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642) 
9  Ciudad Autónoma de Buenos Aires (C.A.B.A.), Laboratory of Amyloidosis and Neurodegeneration, Fundación Instituto Leloir-IIBBA-CONICET, Buenos Aires, Argentina (GRID:grid.6612.3) 
10  San Salvador de Jujuy, Ministerio de Salud de la Provincia de Jujuy, Programa del Adulto Mayor, Jujuy, Argentina (GRID:grid.6612.3) 
11  Hospital Interzonal General de Agudos Eva Perón, Buenos Aires, Argentina (GRID:grid.6612.3) 
12  C.A.B.A, Laboratorio de Bioquímica Molecular, Facultad de Medicina, Instituto de Investigaciones Médicas A. Lanari, UBA, Buenos Aires, Argentina (GRID:grid.6612.3) 
13  Universidad de Buenos Aires (UBA), C.A.B.A, Centro de Neuropsiquiatría y Neurología de la Conducta (CENECON), Facultad de Medicina, Buenos Aires, Argentina (GRID:grid.7345.5) (ISNI:0000 0001 0056 1981) 
14  Univ Arturo Jauretche, Neurosciences and Complex Systems Unit (EnyS), CONICET, Hospital El Cruce “Dr. Néstor Kirchner”, Buenos Aires, Argentina (GRID:grid.423606.5) (ISNI:0000 0001 1945 2152) 
15  Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Associazione Oasi Maria Santissima Srl, Troina, Italy (GRID:grid.423606.5) 
16  Experimental Neuropsychobiology Laboratory, Department of Clinical and Behavioural Neurology, Rome, Italy (GRID:grid.423606.5) 
17  IRCCS Santa Lucia Foundation, Department of Clinical and Behavioural Neurology, Neuropsychiatry Laboratory, Rome, Italy (GRID:grid.417778.a) (ISNI:0000 0001 0692 3437) 
18  IRCCS Ospedale Maggiore Policlinico, Neurodegenerative Diseases Center, University of Milan, Centro Dino Ferrari, Fondazione Ca′ Granda, Milan, Italy (GRID:grid.414818.0) (ISNI:0000 0004 1757 8749) 
19  University of Pisa, Department of Experimental and Clinical Medicine, Neurological Institute, Pisa, Italy (GRID:grid.5395.a) (ISNI:0000 0004 1757 3729) 
20  University of Florence, NEUROFARBA (Department of Neuroscience, Psychology, Drug Research and Child Health), Florence, Italy (GRID:grid.8404.8) (ISNI:0000 0004 1757 2304) 
21  University of Florence, NEUROFARBA (Department of Neuroscience, Psychology, Drug Research and Child Health), Florence, Italy (GRID:grid.8404.8) (ISNI:0000 0004 1757 2304); IRCCS ′Don Carlo Gnocchi′, Florence, Italy (GRID:grid.8404.8) 
22  University of Perugia, Section of Gerontology and Geriatrics, Department of Medicine, Perugia, Italy (GRID:grid.9027.c) (ISNI:0000 0004 1757 3630) 
23  IRCCS Casa Sollievo della Sofferenza, Geriatric Unit and Gerontology-Geriatrics Research Laboratory, Department of Medical Sciences, San Giovanni Rotondo, Italy (GRID:grid.413503.0) (ISNI:0000 0004 1757 9135) 
24  University of Parma, Section of Neuroscience, DIMEC, Parma, Italy (GRID:grid.10383.39) (ISNI:0000 0004 1758 0937); FERB, Alzheimer Center, Bergamo, Italy (GRID:grid.479058.7) 
25  University of Bari Aldo Moro, Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs, Bari, Italy (GRID:grid.7644.1) (ISNI:0000 0001 0120 3326) 
26  Instituto de Investigación Sanitaria Hospital la Paz (IdiPAZ), Madrid, Spain (GRID:grid.81821.32) (ISNI:0000 0000 8970 9163); Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain (GRID:grid.413448.e) (ISNI:0000 0000 9314 1427); Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain (GRID:grid.465524.4) 
27  Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain (GRID:grid.413448.e) (ISNI:0000 0000 9314 1427); Autonomous University of Barcelona, Memory Unit, Neurology Department and Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (GRID:grid.7080.f) 
28  ′Marqués de Valdecilla′ University Hospital (University of Cantabria and IDIVAL), Neurology Service and CIBERNED, Santander, Spain (GRID:grid.411325.0) (ISNI:0000 0001 0627 4262) 
29  University of Central Asturias, Molecular Genetics Laboratory-Hospital, Oviedo, Spain (GRID:grid.411325.0) 
30  Hospital Universitario de Gran Canaria Doctor Negrín, Immunology Service, Las Palmas de Gran Canaria, Spain (GRID:grid.411250.3) (ISNI:0000 0004 0399 7109) 
31  Karolinska University Hospital, Genetics Unit, Theme Aging, Solna, Sweden (GRID:grid.24381.3c) (ISNI:0000 0000 9241 5705); Karolinska Institutet, Division of Neurogeriatrics, Department NVS, Solna, Sweden (GRID:grid.465198.7) 
32  Uppsala University, Department of Public Health/Geriatrics, Uppsala, Sweden (GRID:grid.8993.b) (ISNI:0000 0004 1936 9457) 
33  INSERM, U1167, RID-AGE-Risk Factors and Molecular Determinants of Aging-Related Diseases, Lille, France (GRID:grid.457380.d); Institut Pasteur de Lille, Lille, France (GRID:grid.8970.6) (ISNI:0000 0001 2159 9858); U1167-Excellence Laboratory LabEx DISTALZ, University Lille, Lille, France (GRID:grid.503422.2) (ISNI:0000 0001 2242 6780) 
34  Ciudad Autónoma de Buenos Aires (C.A.B.A.), Laboratory of Amyloidosis and Neurodegeneration, Fundación Instituto Leloir-IIBBA-CONICET, Buenos Aires, Argentina (GRID:grid.503422.2) 
35  Hospital Interzonal General de Agudos Eva Perón, Buenos Aires, Argentina (GRID:grid.503422.2) 
36  San Salvador de Jujuy, Ministerio de Salud de la Provincia de Jujuy, Programa del Adulto Mayor, Jujuy, Argentina (GRID:grid.423606.5) 
37  German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany (GRID:grid.424247.3) (ISNI:0000 0004 0438 0426); University of Bonn, Department of Neurodegenerative Diseases and Geriatric Psychiatry, Bonn, Germany (GRID:grid.10388.32) (ISNI:0000 0001 2240 3300) 
38  German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany (GRID:grid.424247.3) (ISNI:0000 0004 0438 0426); University of Cologne, Department of Psychiatry and Psychotherapy, Cologne, Germany (GRID:grid.6190.e) (ISNI:0000 0000 8580 3777) 
39  University of Cologne, Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Cologne, Germany (GRID:grid.6190.e) (ISNI:0000 0000 8580 3777); University of Bonn, Department of Neurodegenerative Diseases and Geriatric Psychiatry, Bonn, Germany (GRID:grid.10388.32) (ISNI:0000 0001 2240 3300) 
Publication year
2019
Publication date
Jan 2019
Publisher
Nature Publishing Group
e-ISSN
21583188
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41398-019-0394-9
ProQuest document ID
2174279274
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.