The Interaction between HLA‐DRB1 and Smoking in Parkinson's Disease Revisited

C. Domenighetti; V. Douillard; P‐E Sugier; A.A.K. Sreelatha; C. Schulte; S. Grover; P. May; D.R. Bobbili; M. Radivojkov‐Blagojevic; P. Lichtner; A.B. Singleton; D.G. Hernandez; C. Edsall; P‐A Gourraud; G.D. Mellick; A. Zimprich; W. Pirker; E. Rogaeva; A.E. Lang; S. Kõks; P. Taba; S. Lesage; A. Brice; J‐C Corvol; M‐C Chartier‐Harlin; E. Mutez; K. Brockmann; A.B. Deutschländer; G.M. Hadjigeorgiou; E. Dardiotis; L. Stefanis; A.M. Simitsi; E.M. Valente; S. Petrucci; S. Duga; L. Straniero; A. Zecchinelli; G. Pezzoli; L. Brighina; C. Ferrarese; G. Annesi; A. Quattrone; M. Gagliardi; H. Matsuo; A. Nakayama; N. Hattori; K. Nishioka; S.J. Chung; Y.J. Kim; P. Kolber; B.P.C. van de Warrenburg; B.R. Bloem; J. Aasly; M. Toft; L. Pihlstrøm; L. Correia Guedes; J.J. Ferreira; S. Bardien; J. Carr; E. Tolosa; M. Ezquerra; P. Pastor; M. Diez‐Fairen; K. Wirdefeldt; N.L. Pedersen; C. Ran; A.C. Belin; A. Puschmann; E. Ygland Rödström; C.E. Clarke; K.E. Morrison; M. Tan; D. KraincMD; L.F. Burbulla; M.J. Farrer; R. Krüger; T. Gasser; M. Sharma; N. Vince; A. Elbaz

doi:10.1002/mds.29133

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The Interaction between HLA‐DRB1 and Smoking in Parkinson's Disease Revisited

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The Interaction between HLA‐DRB1 and Smoking in Parkinson's Disease Revisited

C. Domenighetti, V. Douillard, P‐E Sugier, A.A.K. Sreelatha, C. Schulte, S. Grover, P. May, D.R. Bobbili, M. Radivojkov‐Blagojevic, P. Lichtner, …

Movement Disorders, Vol.37(9), pp.1929-1937

2022

DOI: https://doi.org/10.1002/mds.29133

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Abstract

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.

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Title: The Interaction between HLA‐DRB1 and Smoking in Parkinson's Disease Revisited
Authors/Creators: C. Domenighetti (Author/Creator) - Université Paris-Saclay
V. Douillard (Author/Creator) - Inserm
P‐E Sugier (Author/Creator)
A.A.K. Sreelatha (Author/Creator) - University of Tübingen
C. Schulte (Author/Creator) - Hertie Institute for Clinical Brain Research
S. Grover (Author/Creator) - University of Tübingen
P. May (Author/Creator) - University of Luxembourg
D.R. Bobbili (Author/Creator) - University of Luxembourg
M. Radivojkov‐Blagojevic (Author/Creator)
P. Lichtner (Author/Creator) - Helmholtz Zentrum München
A.B. Singleton (Author/Creator) - Molecular Genetics Section, Laboratory of Neurogenetics, NIA, NIH, Bethesda, Maryland, USA.
D.G. Hernandez (Author/Creator) - Molecular Genetics Section, Laboratory of Neurogenetics, NIA, NIH, Bethesda, Maryland, USA.
C. Edsall (Author/Creator) - Molecular Genetics Section, Laboratory of Neurogenetics, NIA, NIH, Bethesda, Maryland, USA.
P‐A Gourraud (Author/Creator)
G.D. Mellick (Author/Creator) - Griffith University
A. Zimprich (Author/Creator) - Medical University of Vienna
W. Pirker (Author/Creator) - Department of Neurology, Klinik Ottakring, Vienna, Austria.
E. Rogaeva (Author/Creator) - University of Toronto
A.E. Lang (Author/Creator) - University of Toronto
S. Kõks (Author/Creator) - Murdoch University
P. Taba (Author/Creator) - University of Tartu
S. Lesage (Author/Creator) - Department of Neurologie, Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, INSERM, CNRS, Assistance Publique Hôpitaux de Paris, Paris, France.
A. Brice (Author/Creator) - Department of Neurologie, Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, INSERM, CNRS, Assistance Publique Hôpitaux de Paris, Paris, France.
J‐C Corvol (Author/Creator)
M‐C Chartier‐Harlin (Author/Creator)
E. Mutez (Author/Creator) - Université de Lille
K. Brockmann (Author/Creator) - Hertie Institute for Clinical Brain Research
A.B. Deutschländer (Author/Creator) - Ludwig-Maximilians-Universität München
G.M. Hadjigeorgiou (Author/Creator) - University Hospital of Larissa
E. Dardiotis (Author/Creator) - University Hospital of Larissa
L. Stefanis (Author/Creator) - Eginition Hospital
A.M. Simitsi (Author/Creator) - Eginition Hospital
E.M. Valente (Author/Creator) - University of Pavia
S. Petrucci (Author/Creator) - Advanced Cell Diagnostics (United States)
S. Duga (Author/Creator) - Humanitas University
L. Straniero (Author/Creator) - Humanitas University
A. Zecchinelli (Author/Creator) - Azienda Socio Sanitaria Territoriale Lariana
G. Pezzoli (Author/Creator) - Grigioni Foundation for Parkinson's disease
L. Brighina (Author/Creator) - Azienda Ospedaliera San Gerardo
C. Ferrarese (Author/Creator) - Azienda Ospedaliera San Gerardo
G. Annesi (Author/Creator) - Institute for Biomedical Research and Innovation
A. Quattrone (Author/Creator) - Magna Graecia University
M. Gagliardi (Author/Creator) - Institute of Molecular Bioimaging and Physiology
H. Matsuo (Author/Creator) - National Defense Medical College
A. Nakayama (Author/Creator) - National Defense Medical College
N. Hattori (Author/Creator) - Juntendo University
K. Nishioka (Author/Creator) - Juntendo University
S.J. Chung (Author/Creator) - University of Ulsan
Y.J. Kim (Author/Creator) - Yonsei University
P. Kolber (Author/Creator) - Centre Hospitalier de Luxembourg
B.P.C. van de Warrenburg (Author/Creator) - Radboud University Nijmegen
B.R. Bloem (Author/Creator) - Radboud University Nijmegen
J. Aasly (Author/Creator) - Norwegian University of Science and Technology
M. Toft (Author/Creator) - Oslo University Hospital
L. Pihlstrøm (Author/Creator) - Oslo University Hospital
L. Correia Guedes (Author/Creator)
J.J. Ferreira (Author/Creator) - University of Lisbon
S. Bardien (Author/Creator) - Stellenbosch University
J. Carr (Author/Creator) - Stellenbosch University
E. Tolosa (Author/Creator) - Universitat de Barcelona
M. Ezquerra (Author/Creator) - Universitat de Barcelona
P. Pastor (Author/Creator) - Fundació Clínic per a la Recerca Biomèdica
M. Diez‐Fairen (Author/Creator)
K. Wirdefeldt (Author/Creator) - Karolinska Institutet
N.L. Pedersen (Author/Creator) - Karolinska Institutet
C. Ran (Author/Creator) - Karolinska Institutet
A.C. Belin (Author/Creator) - Karolinska Institutet
A. Puschmann (Author/Creator) - Lund University
E. Ygland Rödström (Author/Creator)
C.E. Clarke (Author/Creator) - Sandwell & West Birmingham Hospitals NHS Trust
K.E. Morrison (Author/Creator) - Queen's University Belfast
M. Tan (Author/Creator) - UCL Institute of Neurology
D. KraincMD (Author/Creator) - Northwestern University
L.F. Burbulla (Author/Creator) - Northwestern University
M.J. Farrer (Author/Creator) - McKnight Brain Institute
R. Krüger (Author/Creator) - University of Luxembourg
T. Gasser (Author/Creator) - Hertie Institute for Clinical Brain Research
M. Sharma (Author/Creator) - University of Tübingen
N. Vince (Author/Creator) - Inserm
A. Elbaz (Author/Creator) - Université Paris-Saclay
Publication Details: Movement Disorders, Vol.37(9), pp.1929-1937
Publisher: Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Identifiers: 991005543246807891
Copyright: © 2022 The Authors.
Murdoch Affiliation: Centre for Molecular Medicine and Innovative Therapeutics
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.52 Neurodegenerative Diseases; 1.52.67 Parkinson's Disease
Web Of Science research areas: Clinical Neurology
ESI research areas: Neuroscience & Behavior