Journal Article

DZNE-2022-01348

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The Interaction between HLA-DRB1 and Smoking in Parkinson's Disease Revisited.

Domenighetti, C. ; Douillard, V. ; Sugier, P.-E. ; Sreelatha, A. A. K. ; Schulte, C.DZNE* ; Grover, S. ; May, P. ; Bobbili, D. R. ; Radivojkov-Blagojevic, M. ; Lichtner, P. ; Singleton, A. B. ; Hernandez, D. M. G.Extern* ; Edsall, C. ; Gourraud, P.-A. ; Mellick, G. D. ; Zimprich, A. ; Pirker, W. ; Rogaeva, E. ; Lang, A. E. ; Koks, S. ; Taba, P. ; Lesage, S. ; Brice, A. ; Corvol, J.-C. ; Chartier-Harlin, M.-C. ; Mutez, E. ; Brockmann, K.DZNE* ; 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. ; Toft, M. ; 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. ; Ygland Rödström, E. ; Clarke, C. E. ; Morrison, K. E. ; Tan, M. ; KraincMD, D. ; Burbulla, L. F.DZNE* ; Farrer, M. J. ; Krüger, R.Extern* ; Gasser, T.DZNE* ; Sharma, M.Extern* ; Vince, N. ; Elbaz, A. ; Genetics, C. U. R. F. A. f. ; Disease, E. i. P. (Collaboration Author)

2022
Wiley New York, NY

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Please use a persistent id in citations: doi:10.1002/mds.29133

Abstract: Two studies that examined the interaction between HLA-DRB1 and smoking in Parkinson's disease (PD) yielded findings in opposite directions.To perform a large-scale independent replication of the HLA-DRB1 × smoking interaction.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.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.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.

Keyword(s): Genetic Predisposition to Disease (MeSH) ; HLA-DRB1 Chains: genetics (MeSH) ; Humans (MeSH) ; Parkinson Disease: genetics (MeSH) ; Polymorphism, Single Nucleotide: genetics (MeSH) ; Smoking: genetics (MeSH) ; HLA ; Parkinson's disease ; gene-environment interaction ; smoking

Note: CC BY-NC

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Contributing Institute(s):

1. Parkinson Genetics (AG Gasser)
2. Translational Disease Modeling (AG Burbulla)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2022

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Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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