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

The interaction between HLA-DRB1 and smoking in Parkinson's disease revisited.

Mov. Disord. 37, 1929-1937 (2022)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Hla ; Parkinson's Disease ; Gene-environment Interaction ; Smoking
ISSN (print) / ISBN 0885-3185
e-ISSN 1531-8257
Journal Movement Disorders
Quellenangaben Volume: 37, Issue: 9, Pages: 1929-1937 Article Number: , Supplement: ,
Publisher Wiley
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)
Grants Université Paris-Saclay
Karolinska Institutet Research Fund
Italian Ministry of Health
Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Service
German Research Council
Fonds National de Recherche (FNR) Luxembourg
EU Joint Program for Neurodegenerative Disease research (JPND)
Estonian Research Council Grant
DFG Research Units FOR2715
DFG Research Units FOR2488
Marta Lundkvist Foundation
Medical Research Council
Michael J. Fox Foundation for Parkinson's Research
UK Medical Research Council
Swedish Research Council
Swedish Brain Foundation
Spanish Ministry of Science and Innovation
South African Medical Research Council
Parkinson's UK
NIH HHS
MSWA
MSA Coalition
Canadian Consortium on Neurodegeneration in Aging