Reference : The Interaction between HLA-DRB1 and Smoking in Parkinson's Disease Revisited

	Document type :	Scientific journals : Article
	Discipline(s) :	Life sciences : Genetics & genetic processes Human health sciences : Neurology
	Focus Areas :	Systems Biomedicine
	To cite this reference:	http://hdl.handle.net/10993/51865

Title :	The Interaction between HLA-DRB1 and Smoking in Parkinson's Disease Revisited
Language :	English
Author, co-author :	Domenighetti, Cloé [> >]
	Douillard, Venceslas [> >]
	Sugier, Pierre-Emmanuel [> >]
	Sreelatha, Ashwin Ashok Kumar [> >]
	Schulte, Claudia [> >]
	Grover, Sandeep [> >]
	May, Patrick [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core]
	Bobbili, Dheeraj Reddy [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core]
	Radivojkov-Blagojevic, Milena [> >]
	Lichtner, Peter [> >]
	Singleton, Andrew B. [> >]
	Hernandez, Dena G. [> >]
	Edsall, Connor [> >]
	Gourraud, Pierre-Antoine [> >]
	Mellick, George D. [> >]
	Zimprich, Alexander [> >]
	Pirker, Walter [> >]
	Rogaeva, Ekaterina [> >]
	Lang, Anthony E. [> >]
	Koks, Sulev [> >]
	Taba, Pille [> >]
	Lesage, Suzanne [> >]
	Brice, Alexis [> >]
	Corvol, Jean-Christophe [> >]
	Chartier-Harlin, Marie-Christine [> >]
	Mutez, Eugénie [> >]
	Brockmann, Kathrin [> >]
	Deutschländer, Angela B. [> >]
	Hadjigeorgiou, Georges M. [> >]
	Dardiotis, Efthimos [> >]
	Stefanis, Leonidas [> >]
	Simitsi, Athina Maria [> >]
	Valente, Enza Maria [> >]
	Petrucci, Simona [> >]
	Duga, Stefano [> >]
	Straniero, Letizia [> >]
	Zecchinelli, Anna [> >]
	Pezzoli, Gianni [> >]
	Brighina, Laura [> >]
	Ferrarese, Carlo [> >]
	Annesi, Grazia [> >]
	Quattrone, Andrea [> >]
	Gagliardi, Monica [> >]
	Matsuo, Hirotaka [> >]
	Nakayama, Akiyoshi [> >]
	Hattori, Nobutaka [> >]
	Nishioka, Kenya [> >]
	Chung, Sun Ju [> >]
	Kim, Yun Joong [> >]
	Kolber, Pierre [> >]
	van de Warrenburg, Bart P. C. [> >]
	Bloem, Bastiaan R. [> >]
	Aasly, Jan [> >]
	Toft, Mathias [> >]
	Pihlstrøm, Lasse [> >]
	Correia Guedes, Leonor [> >]
	Ferreira, Joaquim J. [> >]
	Bardien, Soraya [> >]
	Carr, Jonathan [> >]
	Tolosa, Eduardo [> >]
	Ezquerra, Mario [> >]
	Pastor, Pau [> >]
	Diez-Fairen, Monica [> >]
	Wirdefeldt, Karin [> >]
	Pedersen, Nancy L. [> >]
	Ran, Caroline [> >]
	Belin, Andrea C. [> >]
	Puschmann, Andreas [> >]
	Ygland Rödström, Emil [> >]
	Clarke, Carl E. [> >]
	Morrison, Karen E. [> >]
	Tan, Manuela [> >]
	KraincMD, Dimitri [> >]
	Burbulla, Lena F. [> >]
	Farrer, Matt J. [> >]
	Krüger, Rejko [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience]
	Gasser, Thomas [> >]
	Sharma, Manu [> >]
	Vince, Nicolas [> >]
	Elbaz, Alexis [> >]
	Genetics, Comprehensive Unbiased Risk Factor Assessment For [> >]
	Consortium, Environment In Parkinson S Disease Courage-P. D. [> >]
Publication date :	10-Jul-2022
Journal title :	Movement Disorders
Peer reviewed :	Yes
Audience :	International
Keywords :	[en] Parkinson's disease ; smoking ; gene-environment interaction ; HLA
Abstract :	[en] 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. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Research centres :	Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) ; Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group)
Funders :	Fonds National de la Recherche - FnR
Name of the research project :	Courage-PD, NCER-PD
Target :	Researchers ; Professionals
Permalink :	http://hdl.handle.net/10993/51865
DOI :	10.1002/mds.29133
Other URL :	https://movementdisorders.onlinelibrary.wiley.com/doi/abs/10.1002/mds.29133
FnR project :	FnR ; FNR7490270 > Rudi Balling > COURAGE-PD > Comprehensive Unbiased Risk Factor Assessment For Genetics And Environment In Parkinson‘S Disease > 01/03/2014 > 28/02/2017 > 2013

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