Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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

Domenighetti, Cloé ; Puschmann, Andreas LU orcid ; Ygland Rödström, Emil LU and Elbaz, Alexis (2022) In Movement Disorders 37(9). p.1929-1937
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%... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; and
author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Movement Disorders
volume
37
issue
9
pages
1929 - 1937
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:35810454
  • scopus:85133891525
ISSN
0885-3185
DOI
10.1002/mds.29133
language
English
LU publication?
yes
additional info
© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
id
0987839b-d689-4e9b-aa40-76e98b0cb6ca
date added to LUP
2022-08-16 15:17:14
date last changed
2024-04-18 13:11:19
@article{0987839b-d689-4e9b-aa40-76e98b0cb6ca,
  abstract     = {{<p>BACKGROUND: Two studies that examined the interaction between HLA-DRB1 and smoking in Parkinson's disease (PD) yielded findings in opposite directions.</p><p>OBJECTIVE: To perform a large-scale independent replication of the HLA-DRB1 × smoking interaction.</p><p>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.</p><p>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.</p><p>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.</p>}},
  author       = {{Domenighetti, Cloé and Puschmann, Andreas and Ygland Rödström, Emil and Elbaz, Alexis}},
  issn         = {{0885-3185}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{9}},
  pages        = {{1929--1937}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Movement Disorders}},
  title        = {{The Interaction between HLA-DRB1 and Smoking in Parkinson's Disease Revisited}},
  url          = {{http://dx.doi.org/10.1002/mds.29133}},
  doi          = {{10.1002/mds.29133}},
  volume       = {{37}},
  year         = {{2022}},
}