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

Cloé Domenighetti¹, Venceslas Douillard², Pierre-Emmanuel Sugier¹, Ashwin Ashok Kumar Sreelatha³, Claudia Schulte^{4

5}, Sandeep Grover³, Patrick May⁶, Dheeraj R Bobbili⁶, Milena Radivojkov-Blagojevic⁷, Peter Lichtner⁷, Andrew B Singleton^{8

9}, Dena G Hernandez⁸, Connor Edsall⁸, Pierre-Antoine Gourraud², George D Mellick¹⁰, Alexander Zimprich¹¹, Walter Pirker¹², Ekaterina Rogaeva¹³, Anthony E Lang^{13

14

15

16}, Sulev Koks^{17

18}, Pille Taba^{19

20}, Suzanne Lesage²¹, Alexis Brice²¹, Jean-Christophe Corvol^{21

22}, Marie-Christine Chartier-Harlin²³, Eugénie Mutez²³, Kathrin Brockmann^{4

5}, Angela B Deutschländer^{24

25

26}, Georges M Hadjigeorgiou^{27

28}, Efthimos Dardiotis²⁷, Leonidas Stefanis^{29

30}, Athina Maria Simitsi²⁹, Enza Maria Valente^{31

32}, Simona Petrucci^{33

34}, Stefano Duga^{35

36}, Letizia Straniero³⁵, Anna Zecchinelli³⁷, Gianni Pezzoli³⁸, Laura Brighina^{39

40}, Carlo Ferrarese^{39

40}, Grazia Annesi⁴¹, Andrea Quattrone⁴², Monica Gagliardi⁴³, Hirotaka Matsuo⁴⁴, Akiyoshi Nakayama⁴⁴, Nobutaka Hattori⁴⁵, Kenya Nishioka⁴⁵, Sun Ju Chung⁴⁶, Yun Joong Kim⁴⁷, Pierre Kolber⁴⁸, Bart P C van de Warrenburg⁴⁹, Bastiaan R Bloem⁴⁹, Jan Aasly⁵⁰, Mathias Toft⁵¹, Lasse Pihlstrøm⁵¹, Leonor Correia Guedes^{52

53}, Joaquim J Ferreira^{52

54}, Soraya Bardien⁵⁵, Jonathan Carr⁵⁶, Eduardo Tolosa^{57

58}, Mario Ezquerra⁵⁹, Pau Pastor^{60

61}, Monica Diez-Fairen^{60

61}, Karin Wirdefeldt^{62

63}, Nancy L Pedersen⁶³, Caroline Ran⁶⁴, Andrea C Belin⁶⁴, Andreas Puschmann⁶⁵, Emil Ygland Rödström⁶⁵, Carl E Clarke⁶⁶, Karen E Morrison⁶⁷, Manuela Tan⁶⁸, Dimitri Krainc⁶⁹, Lena F Burbulla^{69

70

71

72}, Matt J Farrer⁷³, Rejko Krüger^{6

48

74

75}, Thomas Gasser^{4

5}, Manu Sharma³, Nicolas Vince², Alexis Elbaz¹; Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (Courage-PD) Consortium

Affiliations

¹ Université Paris-Saclay, UVSQ, Univ. Paris-Sud, Inserm, Team "Exposome, Heredity, Cancer, and Health", CESP, Villejuif, France.
² Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, Nantes, France.
³ Centre for Genetic Epidemiology, Institute for Clinical Epidemiology, and Applied Biometry, University of Tubingen, Tübingen, Germany.
⁴ Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tubingen, Tübingen, Germany.
⁵ German Center for Neurodegenerative Diseases (DZNE), Tubingen, Germany.
⁶ Translational Neuroscience, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg.
⁷ Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
⁸ Molecular Genetics Section, Laboratory of Neurogenetics, NIA, NIH, Bethesda, Maryland, USA.
⁹ Center For Alzheimer's and Related Dementias, NIA, NIH, Bethesda, Maryland, USA.
¹⁰ Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland, Australia.
¹¹ Department of Neurology, Medical University of Vienna, Wien, Austria.
¹² Department of Neurology, Klinik Ottakring, Vienna, Austria.
¹³ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
¹⁴ Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN, Toronto, Ontario, Canada.
¹⁵ Division of Neurology, University of Toronto, Toronto, Ontario, Canada.
¹⁶ Krembil Brain Institute, Toronto, Ontario, Canada.
¹⁷ Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Murdoch, Australia.
¹⁸ Perron Institute for Neurological and Translational Science, Nedlands, Western Australia, Australia.
¹⁹ Department of Neurology and Neurosurgery, University of Tartu, Tartu, Estonia.
²⁰ Neurology Clinic, Tartu University Hospital, Tartu, Estonia.
²¹ Department of Neurologie, Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, INSERM, CNRS, Assistance Publique Hôpitaux de Paris, Paris, France.
²² Assistance Publique Hôpitaux de Paris, Department of Neurology, CIC Neurosciences, Paris, France.
²³ Univ. Lille, Inserm, CHU Lille, UMR-S 1172 - LilNCog- Centre de Recherche Lille Neurosciences and Cognition, Lille, France.
²⁴ Department of Neurology, Ludwig Maximilians University of Munich, Munich, Germany.
²⁵ Department of Neurology, Max Planck Institute of Psychiatry, Munich, Germany.
²⁶ Department of Neurology and Department of Clinical Genomics, Mayo Clinic Florida, Jacksonville, Florida, USA.
²⁷ Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, Larissa, Greece.
²⁸ Department of Neurology, Medical School, University of Cyprus, Nicosia, Cyprus.
²⁹ 1st Department of Neurology, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
³⁰ Center of Clinical Research, Experimental Surgery, and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
³¹ Department of Molecular Medicine, University of Pavia, Pavia, Italy.
³² Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Mondino Foundation, Pavia, Italy.
³³ UOC Medical Genetics and Advanced Cell Diagnostics, S. Andrea University Hospital, Rome, Italy.
³⁴ Department of Clinical and Molecular Medicine, University of Rome, Rome, Italy.
³⁵ Department of Biomedical Sciences, Humanitas University, Milan, Italy.
³⁶ Humanitas Clinical and Research Center, IRCCS, Milan, Italy.
³⁷ Parkinson Institute, Azienda Socio Sanitaria Territoriale (ASST) Gaetano Pini/CTO, Milan, Italy.
³⁸ Parkinson Institute, Fontazione Grigioni, Milan, Italy.
³⁹ Department of Neurology, San Gerardo Hospital, Monza, Italy.
⁴⁰ Department of Medicine and Surgery and Milan Center for Neuroscience, University of Milano Bicocca, Milan, Italy.
⁴¹ Institute for Biomedical Research and Innovation, National Research Council, Cosenza, Italy.
⁴² Institute of Neurology, Magna Graecia University, Catanzaro, Italy.
⁴³ Institute of Molecular Bioimaging and Physiology National Research Council, Catanzaro, Italy.
⁴⁴ Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Saitama, Japan.
⁴⁵ Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
⁴⁶ Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
⁴⁷ Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea.
⁴⁸ Neurology, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg.
⁴⁹ Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Radboud University Medical Centre, Nijmegen, The Netherlands.
⁵⁰ Department of Neurology, St Olav's Hospital and Norwegian University of Science and Technology, Trondheim, Norway.
⁵¹ Department of Neurology, Oslo University Hospital, Oslo, Norway.
⁵² Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
⁵³ Department of Neurosciences and Mental Health, Neurology, Hospital de Santa Maria, Centro Hospitalar Universitario Lisboa Norte (CHULN), Lisbon, Portugal.
⁵⁴ Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
⁵⁵ Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.
⁵⁶ Division of Neurology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.
⁵⁷ Parkinson's Disease and Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
⁵⁸ Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED: CB06/05/0018-ISCIII) Barcelona, Barcelona, Spain.
⁵⁹ Lab of Parkinson Disease and Other Neurodegenerative Movement Disorders, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Institut de Neurociències, Universitat de Barcelona, Barcelona, Catalonia, Spain.
⁶⁰ Fundació per la Recerca Biomèdica i Social Mútua Terrassa, Barcelona, Spain.
⁶¹ Movement Disorders Unit, Department of Neurology, Hospital Universitari Mutua de Terrassa, Barcelona, Spain.
⁶² Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁶³ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁶⁴ Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁶⁵ Department of Clinical Sciences Lund, Neurology, Lund University, Skåne University Hospital, Lund, Sweden.
⁶⁶ University of Birmingham and Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, United Kingdom.
⁶⁷ Faculty of Medicine, Health and Life Sciences, Queens University, Belfast, United Kingdom.
⁶⁸ Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom.
⁶⁹ Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
⁷⁰ Metabolic Biochemistry, Biomedical Center (BMC), Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
⁷¹ Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
⁷² German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
⁷³ Department of Neurology, McKnight Brain Institute, University of Florida, Gainesville, Florida, USA.
⁷⁴ Parkinson's Research Clinic, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg.
⁷⁵ Transversal Translational Medicine, Luxembourg Institute of Health (LIH), Strassen, Luxembourg.

PMID: 35810454
PMCID: PMC9597672
DOI: 10.1002/mds.29133

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

Cloé Domenighetti et al. Mov Disord. 2022 Sep.

. 2022 Sep;37(9):1929-1937.

doi: 10.1002/mds.29133. Epub 2022 Jul 10.

Authors

Affiliations

¹ Université Paris-Saclay, UVSQ, Univ. Paris-Sud, Inserm, Team "Exposome, Heredity, Cancer, and Health", CESP, Villejuif, France.
² Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, Nantes, France.
³ Centre for Genetic Epidemiology, Institute for Clinical Epidemiology, and Applied Biometry, University of Tubingen, Tübingen, Germany.
⁴ Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tubingen, Tübingen, Germany.
⁵ German Center for Neurodegenerative Diseases (DZNE), Tubingen, Germany.
⁶ Translational Neuroscience, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg.
⁷ Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
⁸ Molecular Genetics Section, Laboratory of Neurogenetics, NIA, NIH, Bethesda, Maryland, USA.
⁹ Center For Alzheimer's and Related Dementias, NIA, NIH, Bethesda, Maryland, USA.
¹⁰ Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland, Australia.
¹¹ Department of Neurology, Medical University of Vienna, Wien, Austria.
¹² Department of Neurology, Klinik Ottakring, Vienna, Austria.
¹³ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
¹⁴ Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN, Toronto, Ontario, Canada.
¹⁵ Division of Neurology, University of Toronto, Toronto, Ontario, Canada.
¹⁶ Krembil Brain Institute, Toronto, Ontario, Canada.
¹⁷ Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Murdoch, Australia.
¹⁸ Perron Institute for Neurological and Translational Science, Nedlands, Western Australia, Australia.
¹⁹ Department of Neurology and Neurosurgery, University of Tartu, Tartu, Estonia.
²⁰ Neurology Clinic, Tartu University Hospital, Tartu, Estonia.
²¹ Department of Neurologie, Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, INSERM, CNRS, Assistance Publique Hôpitaux de Paris, Paris, France.
²² Assistance Publique Hôpitaux de Paris, Department of Neurology, CIC Neurosciences, Paris, France.
²³ Univ. Lille, Inserm, CHU Lille, UMR-S 1172 - LilNCog- Centre de Recherche Lille Neurosciences and Cognition, Lille, France.
²⁴ Department of Neurology, Ludwig Maximilians University of Munich, Munich, Germany.
²⁵ Department of Neurology, Max Planck Institute of Psychiatry, Munich, Germany.
²⁶ Department of Neurology and Department of Clinical Genomics, Mayo Clinic Florida, Jacksonville, Florida, USA.
²⁷ Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, Larissa, Greece.
²⁸ Department of Neurology, Medical School, University of Cyprus, Nicosia, Cyprus.
²⁹ 1st Department of Neurology, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
³⁰ Center of Clinical Research, Experimental Surgery, and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
³¹ Department of Molecular Medicine, University of Pavia, Pavia, Italy.
³² Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Mondino Foundation, Pavia, Italy.
³³ UOC Medical Genetics and Advanced Cell Diagnostics, S. Andrea University Hospital, Rome, Italy.
³⁴ Department of Clinical and Molecular Medicine, University of Rome, Rome, Italy.
³⁵ Department of Biomedical Sciences, Humanitas University, Milan, Italy.
³⁶ Humanitas Clinical and Research Center, IRCCS, Milan, Italy.
³⁷ Parkinson Institute, Azienda Socio Sanitaria Territoriale (ASST) Gaetano Pini/CTO, Milan, Italy.
³⁸ Parkinson Institute, Fontazione Grigioni, Milan, Italy.
³⁹ Department of Neurology, San Gerardo Hospital, Monza, Italy.
⁴⁰ Department of Medicine and Surgery and Milan Center for Neuroscience, University of Milano Bicocca, Milan, Italy.
⁴¹ Institute for Biomedical Research and Innovation, National Research Council, Cosenza, Italy.
⁴² Institute of Neurology, Magna Graecia University, Catanzaro, Italy.
⁴³ Institute of Molecular Bioimaging and Physiology National Research Council, Catanzaro, Italy.
⁴⁴ Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Saitama, Japan.
⁴⁵ Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
⁴⁶ Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
⁴⁷ Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea.
⁴⁸ Neurology, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg.
⁴⁹ Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Radboud University Medical Centre, Nijmegen, The Netherlands.
⁵⁰ Department of Neurology, St Olav's Hospital and Norwegian University of Science and Technology, Trondheim, Norway.
⁵¹ Department of Neurology, Oslo University Hospital, Oslo, Norway.
⁵² Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
⁵³ Department of Neurosciences and Mental Health, Neurology, Hospital de Santa Maria, Centro Hospitalar Universitario Lisboa Norte (CHULN), Lisbon, Portugal.
⁵⁴ Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
⁵⁵ Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.
⁵⁶ Division of Neurology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.
⁵⁷ Parkinson's Disease and Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
⁵⁸ Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED: CB06/05/0018-ISCIII) Barcelona, Barcelona, Spain.
⁵⁹ Lab of Parkinson Disease and Other Neurodegenerative Movement Disorders, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Institut de Neurociències, Universitat de Barcelona, Barcelona, Catalonia, Spain.
⁶⁰ Fundació per la Recerca Biomèdica i Social Mútua Terrassa, Barcelona, Spain.
⁶¹ Movement Disorders Unit, Department of Neurology, Hospital Universitari Mutua de Terrassa, Barcelona, Spain.
⁶² Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁶³ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁶⁴ Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁶⁵ Department of Clinical Sciences Lund, Neurology, Lund University, Skåne University Hospital, Lund, Sweden.
⁶⁶ University of Birmingham and Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, United Kingdom.
⁶⁷ Faculty of Medicine, Health and Life Sciences, Queens University, Belfast, United Kingdom.
⁶⁸ Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom.
⁶⁹ Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
⁷⁰ Metabolic Biochemistry, Biomedical Center (BMC), Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
⁷¹ Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
⁷² German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
⁷³ Department of Neurology, McKnight Brain Institute, University of Florida, Gainesville, Florida, USA.
⁷⁴ Parkinson's Research Clinic, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg.
⁷⁵ Transversal Translational Medicine, Luxembourg Institute of Health (LIH), Strassen, Luxembourg.

PMID: 35810454
PMCID: PMC9597672
DOI: 10.1002/mds.29133

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, P_Interaction = 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.

Keywords: HLA; Parkinson's disease; gene-environment interaction; smoking.

PubMed Disclaimer

Figures

**Figure 1.**
Forest plot of the association between genetically-predicted smoking initiation (inverse variance weighted estimate) and Parkinson’s disease stratified by *HLA-DRB1*

**Figure 2.. Prediction of binding affinity (nM) according to the presence of a valine at position 11 (V11) coded by *HLA-DRB1* alleles and homocitrullination (HC) of alpha-synuclein derived peptides**
* P-values for the comparison versus the reference group (V11−HC−).

See this image and copyright information in PMC

References

1. Hollenbach JA, Norman PJ, Creary LE, et al. A specific amino acid motif of HLA-DRB1 mediates risk and interacts with smoking history in Parkinson’s disease. Proc Natl Acad Sci U S A 2019;116:7419–7424. - PMC - PubMed
1. Naito T, Satake W, Ogawa K, et al. Trans-Ethnic Fine-Mapping of the Major Histocompatibility Complex Region Linked to Parkinson’s Disease. Mov Disord 2021;36:1805–1814. - PMC - PubMed
1. Yu E, Ambati A, Andersen MS, et al. Fine mapping of the HLA locus in Parkinson’s disease in Europeans. NPJ Parkinsons Dis 2021;7:84. - PMC - PubMed
1. Hedström AK, Hillert J, Brenner N, et al. DRB1-environment interactions in multiple sclerosis etiology: results from two Swedish case-control studies. J Neurol Neurosurg Psychiatry 2021;92:717–722. - PMC - PubMed
1. Karlson EW, Chang SC, Cui J, et al. Gene-environment interaction between HLA-DRB1 shared epitope and heavy cigarette smoking in predicting incident rheumatoid arthritis. Ann Rheum Dis 2010;69:54–60. - PMC - PubMed

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

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

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