The Interaction between HLA-DRB1 and Smoking in Parkinson's Disease Revisited.
HLA
Parkinson's disease
gene-environment interaction
smoking
Journal
Movement disorders : official journal of the Movement Disorder Society
ISSN: 1531-8257
Titre abrégé: Mov Disord
Pays: United States
ID NLM: 8610688
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
revised:
09
05
2022
received:
21
02
2022
accepted:
06
06
2022
pubmed:
11
7
2022
medline:
16
9
2022
entrez:
10
7
2022
Statut:
ppublish
Résumé
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, P 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.
Sections du résumé
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, 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.
Identifiants
pubmed: 35810454
doi: 10.1002/mds.29133
pmc: PMC9597672
mid: NIHMS1815148
doi:
Substances chimiques
HLA-DRB1 Chains
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1929-1937Subventions
Organisme : Intramural NIH HHS
ID : Z01 AG000949
Pays : United States
Organisme : Medical Research Council
Pays : United Kingdom
Informations de copyright
© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Références
Neurology. 2019 Oct 8;93(15):e1412-e1424
pubmed: 31527283
Ann Rheum Dis. 2010 Jan;69(1):54-60
pubmed: 19151010
Elife. 2018 May 30;7:
pubmed: 29846171
Proc Natl Acad Sci U S A. 2019 Apr 9;116(15):7419-7424
pubmed: 30910980
Nature. 2017 Jun 29;546(7660):656-661
pubmed: 28636593
Wellcome Open Res. 2019 Nov 26;4:186
pubmed: 32760811
Nat Rev Neurol. 2020 Jun;16(6):303-318
pubmed: 32332985
J Parkinsons Dis. 2022;12(1):267-282
pubmed: 34633332
Sci Rep. 2021 Jul 7;11(1):13980
pubmed: 34234189
J Proteome Res. 2020 Jun 5;19(6):2304-2315
pubmed: 32308001
Ann Neurol. 2017 Nov;82(5):655-664
pubmed: 28981958
J Parkinsons Dis. 2021;11(4):1981-1993
pubmed: 34275906
J Neurol Neurosurg Psychiatry. 2021 Jul;92(7):717-722
pubmed: 33687974
Mov Disord. 2021 Aug;36(8):1805-1814
pubmed: 33973677
NPJ Parkinsons Dis. 2021 Sep 21;7(1):84
pubmed: 34548497
Pharmacogenomics J. 2014 Apr;14(2):192-200
pubmed: 23712092
Nat Genet. 2019 Feb;51(2):237-244
pubmed: 30643251
Am J Epidemiol. 2017 Apr 15;185(8):681-687
pubmed: 28369180