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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
The Interaction between HLA-DRB1 and Smoking in Parkinson's Disease Revisited
Movement Disorders, Year 2022
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Description
Background: Two studies that examined the interaction between HLA-DRB1 and smoking in Parkinson's disease (PD) yielded findings in opposite directions. Objective: To perform a large-scale independent replication of the HLA-DRB1 × smoking interaction. Methods: We genotyped 182 single nucleotide polymorphism (SNPs) associated with smoking initiation in 12 424 cases and 9480 controls to perform a Mendelian randomization (MR) analysis in strata defined by HLA-DRB1. Results: At the amino acid level, a valine at position 11 (V11) in HLA-DRB1 displayed the strongest association with PD. MR showed an inverse association between genetically predicted smoking initiation and PD only in absence of V11 (odds ratio, 0.74, 95% confidence interval, 0.59–0.93, PInteraction = 0.028). In silico predictions of the influence of V11 and smoking-induced modifications of α-synuclein on binding affinity showed findings consistent with this interaction pattern. Conclusions: Despite being one of the most robust findings in PD research, the mechanisms underlying the inverse association between smoking and PD remain unknown. Our findings may help better understand this association. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Authors & Co-Authors
Domenighetti, Cloe
France, Versailles
Université de Versailles Saint-quentin-en-yvelines
Douillard, Venceslas
France, Nantes
Nantes Université
Sugier, Pierre Emmanuel
France, Versailles
Université de Versailles Saint-quentin-en-yvelines
Sreelatha, Ashwin Ashok Kumar
Germany, Tubingen
Eberhard Karls Universität Tübingen
Schulte, Claudia M.S.
Germany, Tubingen
Hertie-institut Für Klinische Hirnforschung
Germany, Bonn
Deutsches Zentrum Für Neurodegenerative Erkrankungen
Grover, Sandeep
Germany, Tubingen
Eberhard Karls Universität Tübingen
May, Patrick
Luxembourg, Esch-sur-alzette
University of Luxembourg
Bobbili, Dheeraj Reddy
Luxembourg, Esch-sur-alzette
University of Luxembourg
Radivojkov-Blagojević, Milena
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Lichtner, Peter K.
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Singleton, Andrew B.
United States, Bethesda
National Institute on Aging Nia
Hernandez, Dena G.
United States, Bethesda
National Institute on Aging Nia
Edsall, Connor
United States, Bethesda
National Institute on Aging Nia
Gourraud, Pierre Antoine F.
France, Nantes
Nantes Université
Mellick, George D.
Australia, Brisbane
Griffith University
Zimprich, Alexander
Austria, Vienna
Medizinische Universität Wien
Pirker, Walter
Austria, Vienna
Klinik Ottakring
Rogaeva, Ekaterina A.
Canada, Toronto
Tanz Centre for Research in Neurodegenerative Diseases
Lang, Anthony E.
Canada, Toronto
Tanz Centre for Research in Neurodegenerative Diseases
Canada, Toronto
Toronto Western Hospital University of Toronto
Canada, Toronto
University of Toronto
Canada, Toronto
Krembil Brain Institute
Kõks, Sulev V.
Australia, Perth
Murdoch University
Australia, Nedlands
Perron Institute for Neurological and Translational Science
Taba, Pille
Estonia, Tartu
Tartu Ülikool
Estonia, Tartu
Tartu Ülikooli Kliinikum
Lesage, Suzanne
France, Paris
Sorbonne Université
Brice, Alexis
France, Paris
Sorbonne Université
Corvol, Jean Christophe
France, Paris
Sorbonne Université
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Chartier-Harlin, Marie Christine
France, Lille
Université de Lille
Mutez, Eugénie
France, Lille
Université de Lille
Brockmann, Kathrin
Germany, Tubingen
Hertie-institut Für Klinische Hirnforschung
Germany, Bonn
Deutsches Zentrum Für Neurodegenerative Erkrankungen
Deutschländer, Angela B.
Germany, Munich
Ludwig-maximilians-universität München
Germany, Munich
Max Planck Institute of Psychiatry
United States, Jacksonville
Mayo Clinic in Jacksonville, Florida
Hadjigeorgiou, Georgios M.
Greece, Volos
University of Thessaly
Cyprus, Nicosia
University of Cyprus Medical School
Dardiotis, Efthymios
Greece, Volos
University of Thessaly
Stefanis, Leonidas
Greece, Athens
Eginition Hospital
Greece, Athens
Academy of Athens
Simitsi, Athina Maria
Greece, Athens
Eginition Hospital
Valente, Enza Maria
Italy, Pavia
Università Degli Studi Di Pavia
Italy, Pavia
Irccs Fondazione Mondino
Petrucci, Simona
Italy, Rome
Azienda Ospedaliero-universitaria Sant'andrea
Italy, Rome
University of Rome
Duga, Stefano
Italy, Pieve Emanuele
Humanitas University
Italy, Rozzano
Humanitas Research Hospital
Straniero, Letizia
Italy, Pieve Emanuele
Humanitas University
Zecchinelli, A. Lena
Italy, Milan
Istituti Clinici Di Perfezionamento
Pezzoli, Gianni
Italy, Milan
Istituti Clinici Di Perfezionamento
Brighina, Laura
Italy, Monza
Azienda Ospedaliera San Gerardo Monza
Italy, Milan
Università Degli Studi Di Milano-bicocca
Ferrarese, Carlo
Italy, Monza
Azienda Ospedaliera San Gerardo Monza
Italy, Milan
Università Degli Studi Di Milano-bicocca
Annesi, Grazia
Italy, Rome
Consiglio Nazionale Delle Ricerche
Quattrone, Andrea
Italy, Catanzaro
Università Degli Studi Magna Graecia Di Catanzaro
Gagliardi, Monica
Italy, Catanzaro
Institute of Molecular Bioimaging and Physiology of the National Research Council
Matsuo, Hirotaka
Japan, Tokorozawa
National Defense Medical College Tokorozawa
Nakayama, Akiyoshi
Japan, Tokorozawa
National Defense Medical College Tokorozawa
Hattori, Nobutaka
Japan, Tokyo
Juntendo University School of Medicine
Nishioka, Kenya
Japan, Tokyo
Juntendo University School of Medicine
Chung, Sun-ju
South Korea, Seoul
University of Ulsan College of Medicine
Kim, Yunjoong
South Korea, Seoul
Yonsei University College of Medicine
Kolber, Pierre
Luxembourg, Luxembourg
Centre Hospitalier de Luxembourg
van de Warrenburg, Bart P.C.
Netherlands, Nijmegen
Donders Institute for Brain, Cognition and Behaviour
Bloem, Bastiaan R.
Netherlands, Nijmegen
Donders Institute for Brain, Cognition and Behaviour
Aasly, Jan Olav
Norway, Trondheim
Norges Teknisk-naturvitenskapelige Universitet
Toft, Mathias
Norway, Oslo
Oslo Universitetssykehus
Pihlstrom, Lasse
Norway, Oslo
Oslo Universitetssykehus
Correia-Guedes, Leonor
Portugal, Lisbon
Instituto de Medicina Molecular João Lobo Antunes
Portugal, Lisbon
Universidade de Lisboa
Ferreira, Joaquim José
Portugal, Lisbon
Instituto de Medicina Molecular João Lobo Antunes
Portugal, Lisbon
Faculdade de Medicina, Universidade de Lisboa
Bardien, Soraya
South Africa, Cape Town
Stellenbosch University, Faculty of Medicine and Health Sciences
Carr, Jonathan A.
South Africa, Cape Town
Stellenbosch University, Faculty of Medicine and Health Sciences
Tolosa, Eduardo S.
Spain, Barcelona
Universitat de Barcelona
Spain, Madrid
Instituto de Salud Carlos Iii
Ezquerra, Mario
Spain, Barcelona
Universitat de Barcelona
Pástor, Pau
Spain, Barcelona
Fundació Per la Recerca Biomèdica I Social Mútua Terrassa
Spain, Terrassa
Mutua de Terrassa
Diez-Fairen, Monica
Spain, Barcelona
Fundació Per la Recerca Biomèdica I Social Mútua Terrassa
Spain, Terrassa
Mutua de Terrassa
Wirdefeldt, Karin
Sweden, Stockholm
Karolinska Institutet
Pedersen, Nancy Lee
Sweden, Stockholm
Karolinska Institutet
Ran, Caroline
Sweden, Stockholm
Karolinska Institutet
Belin, Andrea Carmine
Sweden, Stockholm
Karolinska Institutet
Puschmann, Andreas J.
Sweden, Lund
Neurologi, Lund
Ygland Rödström, Emil
Sweden, Lund
Neurologi, Lund
Clarke, Carl E.
United Kingdom, West Bromwich
Sandwell and West Birmingham Hospitals Nhs Trust
Morrison, Karen E.
United Kingdom, Belfast
Queen's University Belfast
Tan, Manuela M.X.
United Kingdom, London
Ucl Queen Square Institute of Neurology
Krainc, Dimitri
United States, Chicago
Northwestern University Feinberg School of Medicine
Burbulla, Lena F.
United States, Chicago
Northwestern University Feinberg School of Medicine
Germany, Munich
Ludwig-maximilians-universität München
Germany, Munich
Munich Cluster for Systems Neurology Synergy
Germany, Bonn
Deutsches Zentrum Für Neurodegenerative Erkrankungen
Farrer, Matthew J.
United States, Gainesville
University of Florida
Krüger, Rejko
Luxembourg, Esch-sur-alzette
University of Luxembourg
Luxembourg, Luxembourg
Centre Hospitalier de Luxembourg
Luxembourg, Strassen
Luxembourg Institute of Health
Gasser, Thomas
Germany, Tubingen
Hertie-institut Für Klinische Hirnforschung
Germany, Bonn
Deutsches Zentrum Für Neurodegenerative Erkrankungen
Sharma, Manu
Germany, Tubingen
Eberhard Karls Universität Tübingen
Vince, Nicolas
France, Nantes
Nantes Université
Elbaz, Alexis
France, Versailles
Université de Versailles Saint-quentin-en-yvelines
Statistics
Citations: 80
Authors: 80
Affiliations: 66
Identifiers
Doi:
10.1002/mds.29133
ISSN:
08853185
e-ISSN:
15318257
Study Design
Randomised Control Trial
Case-Control Study