The Interaction between <i>HLA-DRB1</i> and Smoking in Parkinson's Disease Revisited



Domenighetti, Cloe, Douillard, Venceslas, Sugier, Pierre-Emmanuel, Sreelatha, Ashwin Ashok Kumar, Schulte, Claudia, Grover, Sandeep, May, Patrick, Bobbili, Dheeraj R, Radivojkov-Blagojevic, Milena, Lichtner, Peter
et al (show 70 more authors) (2022) The Interaction between <i>HLA-DRB1</i> and Smoking in Parkinson's Disease Revisited. MOVEMENT DISORDERS, 37 (9). pp. 1929-1937.

Access the full-text of this item by clicking on the Open Access link.

Abstract

<h4>Background</h4>Two studies that examined the interaction between HLA-DRB1 and smoking in Parkinson's disease (PD) yielded findings in opposite directions.<h4>Objective</h4>To perform a large-scale independent replication of the HLA-DRB1 × smoking interaction.<h4>Methods</h4>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.<h4>Results</h4>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, P<sub>Interaction</sub>  = 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.<h4>Conclusions</h4>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.

Item Type: Article
Uncontrolled Keywords: Parkinson's disease, smoking, gene-environment interaction, HLA
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 28 Oct 2022 15:12
Last Modified: 11 Oct 2023 12:31
DOI: 10.1002/mds.29133
Open Access URL: https://doi.org/10.1002/mds.29133
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3165860