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

Domenighetti, Cloé; Douillard, Venceslas; Sugier, Pierre‐Emmanuel; Sreelatha, Ashwin Ashok Kumar; Schulte, Claudia; Grover, Sandeep; Bobbili, Dheeraj Reddy; 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.; Kõks, Sulev; Taba, Pille; Lesage, Suzanne; Brice, Alexis; Corvol, Jean‐Christophe; Chartier‐Harlin, Marie‐Christine; Mutez, Eugénie; Brockmann, Kathrin; Deutschländer, Angela; Hadjigeorgiou, Giorgos 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; Nishioka, Kenya; Chung, Sun Ju; Kim, Yun Joong; Kolber, Pierre; Warrenburg, B.P.C. van de; Bloem, Bastiaan R.; Aasly, Jan; Toft, Mathias; Pihlstrøm, Lasse; Guedes, Leonor Correia; Ferreira, Joaquim J.; Bardien, Soraya; Carr, Jonathan; Tolosa, Eduardo; Ezquerra, Mario; Pástor, Pau; Díez-Fairén, Mónica; Wirdefeldt, Karin; Pedersen, Nancy L.; Ran, Caroline; Belin, Andrea Carmine; Puschmann, Andreas; Rödström, Emil Ygland; Clarke, Carl E; Morrison, Karen E.; Tan, Manuela; KraincMD, Dimitri; Burbulla, Lena F.; Farrer, Matt; Krüger, Rejko; Gasser, Thomas; Sharma, Manu; Vince, Nicolas; Elbaz, Alexis

doi:10.1002/mds.29133

Cited by 8 publications

(2 citation statements)

References 20 publications

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“…In the context of genetic association studies, a parallel effort focused on direct association with HLA polymorphisms to understand the mechanisms in which HLA molecules impact disease susceptibility and severity. These studies have identified protective and risk HLA alleles, such as HLA-DRB1*15:01 in multiple sclerosis (Moutsianas et al 2015), HLA-DRB1*09:01 with tIgE levels in asthma (Vince et al 2020b), specific HLA-DQB1 amino acids in hepatitis C virus infection (Valencia et al 2022), or the HLA-DRB1 valine 11 in Parkinson's disease (Domenighetti et al 2022), among many others. The five most polymorphic HLA genes (HLA-A, HLA-B, HLA-C, HLA-DQB1, and HLA-DRB1) are exceptionally diverse, with almost 30,000 alleles combined (Robinson et al 2020).…”

Section: Introductionmentioning

confidence: 99%

Optimal HLA imputation of admixed population with dimension reduction

Douillard

Silva

Bourguiba‐Hachemi

et al. 2023

Preprint

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Human genomics has quickly evolved, powering genome-wide association studies (GWASs). SNP-based GWASs cannot capture the intense polymorphism of HLA genes, highly associated with disease susceptibility. There are methods to statistically impute HLA genotypes from SNP-genotypes data, but lack of diversity in reference panels hinders their performance. We evaluated the accuracy of the 1,000 Genomes data as a reference panel for imputing HLA from admixed individuals of African and European ancestries, focusing on (a) the full dataset, (b) 10 replications from 6 populations, (c) 19 conditions for the custom reference panels. The full dataset outperformed smaller models, with a good F1-score of 0.66 for HLA-B. However, custom models outperformed the multiethnic or population models of similar size (F1-scores up to 0.53, against up to 0.42). We demonstrated the importance of using genetically specific models for imputing admixed populations, which are currently underrepresented in public datasets, opening the door to HLA imputation for every genetic population.

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Section: Introductionmentioning

confidence: 99%

Optimal HLA imputation of admixed population with dimension reduction

Douillard

Silva

Bourguiba‐Hachemi

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…In the context of genetic association studies, a parallel effort focused on direct association with HLA polymorphisms to understand the mechanisms in which HLA molecules impact disease susceptibility and severity. These studies have identified protective and risk HLA alleles, such as HLA‐DRB1 * 15:01 in multiple sclerosis, 26 HLA‐DRB1 * 09:01 with tIgE levels in asthma, 27 specific HLA‐DQB1 amino acids in hepatitis C virus infection, 28 or the HLA‐DRB1 valine 11 in Parkinson's disease, 29 among many others. The five most polymorphic HLA genes ( HLA‐A , HLA‐B , HLA‐C , HLA‐DQB1 , and HLA‐DRB1 ) are exceptionally diverse, with almost 30,000 alleles combined 30 .…”

Section: Introductionmentioning

confidence: 99%

Optimal population‐specific HLA imputation with dimension reduction

Douillard,

dos Santos Brito Silva,

Bourguiba‐Hachemi

et al. 2023

HLA

Self Cite

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Human genomics has quickly evolved, powering genome‐wide association studies (GWASs). SNP‐based GWASs cannot capture the intense polymorphism of HLA genes, highly associated with disease susceptibility. There are methods to statistically impute HLA genotypes from SNP‐genotypes data, but lack of diversity in reference panels hinders their performance. We evaluated the accuracy of the 1000 Genomes data as a reference panel for imputing HLA from admixed individuals of African and European ancestries, focusing on (a) the full dataset, (b) 10 replications from 6 populations, and (c) 19 conditions for the custom reference panels. The full dataset outperformed smaller models, with a good F1‐score of 0.66 for HLA‐B. However, custom models outperformed the multiethnic or population models of similar size (F1‐scores up to 0.53, against up to 0.42). We demonstrated the importance of using genetically specific models for imputing populations, which are currently underrepresented in public datasets, opening the door to HLA imputation for every genetic population.

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Clearing the Smoke: What Protects Smokers from Parkinson's Disease?

Rose,

Schwarzschild,

Gomperts

2024

Movement Disorders

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The link between smoking and a lower risk of Parkinson's disease (PD) is one of the strongest environmental or lifestyle associations in neuroepidemiology. Growing evidence supports the hypothesis that the association is based on a neuroprotective effect of smoking on PD, despite the plausible alternative that smoking serves as a marker for a proximal protective influence without itself conferring benefit. But how smoking could protect against neurodegeneration in PD is not well understood. Of several candidate molecules and mechanisms that have been nominated, nicotine has received the most attention. However, randomized controlled clinical trials of nicotine in PD have failed to demonstrate benefit on motor endpoints, including the NIC‐PD study in which recently diagnosed participants were randomly assigned to placebo or nicotine treatment for 1 year. Given these results, the time is right to evaluate the neuroprotective potential of other molecules and biochemical cascades triggered by smoking. Here, we review the evidence supporting smoking's possible protective effect on PD, compounds in tobacco and smoke that might mediate such benefit, and non‐causal classes of explanation, including reverse causation and the prospect of shared genetic determinants of smoking and PD resistance. The therapeutic potential of non‐nicotine components of smoke is suggested by studies supporting multiple alternative mechanisms ranging from monoamine oxidase inhibitors to gut microbiome disruption to antioxidant response induction by chronic exposure to low levels of carbon monoxide. Rigorous investigation is warranted to evaluate this molecule and others for disease‐preventing and disease‐modifying activity in PD models and, if warranted, in clinical trials. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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The Interaction betweenHLA‐DRB1and Smoking in Parkinson's Disease Revisited

Abstract: EP1802749 (A2) KASPP (LRRK2) gene, its production and use for the detection and treatment of neurodegenerative disorders issued. A. E. reports grants from ANR, The Michael J. Fox foundation, Plan Ecophyto (French Ministry of Agriculture), and France Parkinson, outside the submitted work.

Cited by 8 publications

References 20 publications

Optimal HLA imputation of admixed population with dimension reduction

Optimal HLA imputation of admixed population with dimension reduction

Optimal population‐specific HLA imputation with dimension reduction

Clearing the Smoke: What Protects Smokers from Parkinson's Disease?

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