Dairy Intake and Parkinson's Disease: A Mendelian Randomization Study

Background Previous prospective studies highlighted dairy intake as a risk factor for Parkinson's disease (PD), particularly in men. It is unclear whether this association is causal or explained by reverse causation or confounding. Objective The aim is to examine the association between genetic...

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Published inMovement disorders Vol. 37; no. 4; pp. 857 - 864
Main Authors Domenighetti, Cloé, Sugier, Pierre‐Emmanuel, Ashok Kumar Sreelatha, Ashwin, Schulte, Claudia, Grover, Sandeep, Mohamed, Océane, Portugal, Berta, May, Patrick, Bobbili, Dheeraj R., Radivojkov‐Blagojevic, Milena, Lichtner, Peter, Singleton, Andrew B., Hernandez, Dena G., Edsall, Connor, Mellick, George D., Zimprich, Alexander, Pirker, Walter, Rogaeva, Ekaterina, Lang, Anthony E., Koks, Sulev, Taba, Pille, Lesage, Suzanne, Brice, Alexis, Corvol, Jean‐Christophe, Chartier‐Harlin, Marie‐Christine, Mutez, Eugénie, Brockmann, Kathrin, Deutschländer, Angela B., Hadjigeorgiou, Georges 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, Kawamura, Yusuke, Hattori, Nobutaka, Nishioka, Kenya, Chung, Sun Ju, Kim, Yun Joong, Kolber, Pierre, Warrenburg, Bart P.C., Bloem, Bastiaan R., Aasly, Jan, Toft, Mathias, Pihlstrøm, Lasse, Correia Guedes, Leonor, Ferreira, Joaquim J., Bardien, Soraya, Carr, Jonathan, Tolosa, Eduardo, Ezquerra, Mario, Pastor, Pau, Diez‐Fairen, Monica, Wirdefeldt, Karin, Pedersen, Nancy L., Ran, Caroline, Belin, Andrea C., Puschmann, Andreas, Hellberg, Clara, Clarke, Carl E., Morrison, Karen E., Tan, Manuela, Krainc, Dimitri, Burbulla, Lena F., Farrer, Matt J., Krüger, Rejko, Gasser, Thomas, Sharma, Manu, Elbaz, Alexis
Format Journal Article
LanguageEnglish
Published Hoboken, USA John Wiley & Sons, Inc 01.04.2022
Wiley Subscription Services, Inc
Wiley
Subjects
Clinical Medicine
dairy intake; Parkinson's disease; Mendelian randomization
Dairy Products - adverse effects
Female
Genetic Predisposition to Disease - genetics
Genome-Wide Association Study
Humans
Klinisk medicin
Lactase
Life Sciences
Male
Medical and Health Sciences
Medicin och hälsovetenskap
Mendelian Randomization Analysis
Movement disorders
Neurodegenerative diseases
Neurologi
Neurology
Neurons and Cognition
Parkinson Disease - epidemiology
Parkinson Disease - genetics
Parkinson's disease
Polymorphism, Single Nucleotide - genetics
Risk Factors
dairy intake; Parkinson's disease; Mendelian randomization
dairy intake
Parkinson's disease
Mendelian randomization
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Summary:Background Previous prospective studies highlighted dairy intake as a risk factor for Parkinson's disease (PD), particularly in men. It is unclear whether this association is causal or explained by reverse causation or confounding. Objective The aim is to examine the association between genetically predicted dairy intake and PD using two‐sample Mendelian randomization (MR). Methods We genotyped a well‐established instrumental variable for dairy intake located in the lactase gene (rs4988235) within the Courage‐PD consortium (23 studies; 9823 patients and 8376 controls of European ancestry). Results Based on a dominant model, there was an association between genetic predisposition toward higher dairy intake and PD (odds ratio [OR] per one serving per day = 1.70, 95% confidence interval = 1.12–2.60, P = 0.013) that was restricted to men (OR = 2.50 [1.37–4.56], P = 0.003; P‐difference with women = 0.029). Conclusions Using MR, our findings provide further support for a causal relationship between dairy intake and higher PD risk, not biased by confounding or reverse causation. Further studies are needed to elucidate the underlying mechanisms. © 2022 International Parkinson and Movement Disorder Society
Bibliography:and serves on the editorial board of Practical Neurology and Digital Biomarkers. M.T. (M. Toft) reports grants from the Research Council of Norway during the conduct of the study and grants from the South‐Eastern Norway Regional Health Authority and The Michael J. Fox Foundation outside the submitted work. L.P. reports grants from the Norwegian Health Association and the South‐Eastern Norway Regional Health Authority outside the submitted work. J.J.F. reports grants from GlaxoSmithKline, Grunenthal, Fundação MSD (Portugal), Teva, MSD, Allergan, Novartis, Medtronic, Lundbeck, Solvay, Bial, Merck‐Serono, Merz, Ipsen, Biogen, Acadia, Allergan, AbbVie, and Sunovion Pharmaceuticals and personal fees from Faculdade de Medicina de Lisboa, CNS—Campus Neurológico Sénior, Bial, and Novartis outside the submitted work. E.T. received honoraria for consultancy from Teva, Bial, Prevail Therapeutics, Boehringer Ingelheim, Roche, and Biogen and has received funding for research from the Spanish Network for Research on Neurodegenerative Disorders (CIBERNED)—Instituto Carlos III (ISCIII) and The Michael J. Fox Foundation for Parkinson's Research (MJFF). K.W. reports grants from the Swedish Research Council during the conduct of the study. N.L.P. reports grants from the Swedish Research Council during the conduct of the study. A.P. reports grants from Parkinsonfonden (The Swedish Parkinson Foundation), ALF (Swedish government), Region Skåne, Sweden, Skåne University Hospital, and Hans‐Gabriel och Trolle Wachtmeister Stiftelse för Medicinsk Forskning, Sweden, Multipark—a strategic research environment at Lund University during the conduct of the study and personal fees from Elsevier outside the submitted work. M.T. (M. Tan) reports grants from Parkinson's UK and others from The Michael J. Fox Foundation and the University College London outside the submitted work. R.K. reports grants from the Fonds National de Recherche (FNR), and the German Research Council (DFG); nonfinancial support from AbbVie and Zambon during the conduct of the study; personal fees from the University of Luxembourg, Luxembourg Institute of Health, and Centre Hospitalier de Luxembourg; grants from the Fonds National de Recherche, Luxembourg (FNR), and Luxembourg/German Research Council (DFG); and personal fees from Desitin/Zambon, AbbVie GmbH, and Medtronic GmbH outside the submitted work. T.G. reports personal fees from UCB Pharma, Novartis, Teva, and MedUpdate; grants from The Michael J. Fox Foundation for Parkinson's Research, Bundesministerium für Bildung und Forschung (BMBF), and Deutsche Forschungsgemeinschaft (DFG); and others from “Joint Programming for Neurodegenerative Diseases” (JPND) program, funded by the European Commission, outside the submitted work; in addition, Dr. Gasser has a patent, patent number: EP1802749 (A2) KASPP (LRRK2) Gene, Its production and Use for the Detection and Treatment of Neurodegenerative Disorders Issued. A.E. reports grants from Agence nationale de recherche (ANR), The Michael J. Fox Foundation, Plan Ecophyto (French Ministry of Agriculture), and France Parkinson outside the submitted work.
https://www.neurodegenerationresearch.eu/initiatives/annual-calls-for-proposals/closed-calls/risk-factors-2012/risk-factor-call-results/courage-pd/
Pediatric Research
Journal of Medical Genetics
Journal of Parkinson's Disease
A.B.S. reports grants from the Department of Defense during the conduct of the study and grants from The Michael J. Fox Foundation outside the submitted work. W.P. reports personal fees from Grünenthal, AbbVie, AOP Orphan, and Zambon; personal fees and others from Boehringer Ingelheim; and personal fees from Stada and UCB Pharma outside the submitted work. A.E.L. reports personal fees from AbbVie, AFFiRis, Janssen, Biogen, Merck, Sun Pharma, Corticobasal Solutions, Sunovion, Paladin, Lilly, Medtronic, Theravance, Lundbeck, Retrophin, Roche, and PhotoPharmics outside the submitted work. A.B. reports grants from France Parkinson + FRC, ANR‐EPIG‐Agence nationale de recherche, ANR—JPND—Agence nationale de recherche, RDS (Roger de Spoelberch Foundation), France Alzheimer, Institut de France, ANR—EPIG, and FMR (maladies rares) outside the submitted work. J.‐C.C. reports grants from The Michael J. Fox Foundation and Sanofi and served on the advisory boards of Air Liquide, Biogen, Denali, Ever Pharma, Idorsia, Prevail Therapeutic, Theranexus, and UCB outside the submitted work. M.‐C.C.‐H. reports grants from France Parkinson, ANR—Agence nationale de recherche (MetDePaDi, Synapark), and ANR–JPND (TransNeuro), Agence nationale de recherche, Grant; Fondation de France, and The Michael J. Fox Foundation outside the submitted work. K.B. reports grants from MJFF and BMBF; personal fees from Zambon, UCB, and AbbVie; and grants from the University of Tubingen outside the submitted work. L.S. over the past year has received the following grants: PPMI2 (supported by The Michael J. Fox Foundation), IMPRIND‐IMI2 number 116060 (EU, H2020), “Transferring Autonomous and Non‐Autonomous Cell Degeneration 3D Models between EU and USA for Development of Effective Therapies for Neurodegenerative Diseases (ND)—CROSS NEUROD” (H2020‐EU 1.3.3., grant number778003); “Chaperone‐Mediated Autophagy in Neurodegeneration” (Hellenic Foundation for Research and Innovation Grant HFRI‐FM17‐3013); and “CMA as a Means to Counteract alpha‐Synuclein Pathology in Non‐Human Primates” Grant by The Michael J. Fox Foundation (collaborator). He is co‐head and Principal Investigator at the NKUA of the General Secretariat of Research and Technology (GSRT)–funded Grant “National Network of Precision Medicine for Neurodegenerative Diseases.” He has served on the advisory boards of AbbVie, ITF Hellas, and Biogen and has received honoraria from AbbVie and Sanofi. There are no specific disclosures related to the current work. E.M.V. serves as associate editor of the
C.D. is the recipient of a doctoral grant from Université Paris‐Saclay, France. P.M. was funded by the Fonds National de Recherche (FNR), Luxembourg, as part of the National Centre of Excellence in Research on Parkinson's Disease (NCER‐PD, FNR11264123) and the DFG Research Units FOR2715 (INTER/DFG/17/11583046) and FOR2488 (INTER/DFG/19/14429377). A.B.S., D.G.H., and C.E. are funded by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services, project ZO1 AG000949. E.R. is funded by the Canadian Consortium on Neurodegeneration in Aging. S.K. is funded by MSWA. P.T. is the recipient of an Estonian Research Council Grant PRG957. E.M.V. is funded by the Italian Ministry of Health (Ricerca Corrente 2021). S.B. and J.C. are supported by grants from the National Research Foundation of South Africa (grant number: 106052); the South African Medical Research Council (Self‐Initiated Research Grant); and Stellenbosch University, South Africa; they also acknowledge the support of the NRF‐DST Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research; and Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town. P.P. and M.D.‐F. have received funding from the Spanish Ministry of Science and Innovation (SAF2013‐47939‐R). K.W. and N.L.P. are funded by the Swedish Research Council, grant numbers K2002‐27X‐14056‐02B, 521‐2010‐2479, 521‐2013‐2488, and 2017‐02175. N.L.P. is funded by the National Institutes of Health, grant numbers ES10758 and AG 08724. C.R. is funded by the Märta Lundkvist Foundation, Swedish Brain Foundation, and Karolinska Institutet Research Fund. A.C.B. is funded by the Swedish Brain Foundation, Swedish Research Council, and Karolinska Institutet Research Funds. M.T. (M. Tan) is funded by the Parkinson's UK. M.S. was supported by grants from the German Research Council (DFG/SH 599/6‐1), MSA Coalition, and The Michael J. Fox Foundation (USA Genetic Diversity in PD Program: GAP‐India Grant ID: 17473). PG GEN sample collection was funded by the MRC and UK Medical Research Council (C.E.C. and K.E.M.). The sponsors had no role in the study design, data collection, data analysis, data interpretation, writing of the report, or decision to submit the paper for publication.
Relevant conflicts of interest/financial disclosures
This study used data from the Courage‐PD consortium, conducted under a partnership agreement among 35 studies. The Courage‐PD consortium is supported by the EU Joint Program for Neurodegenerative Disease research (JPND
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Funding agencies
and member of the editorial board of Movement Disorders Clinical Practice and received grants from the Italian Ministry of Health, CARIPLO Foundation, Pierfranco and Luisa Mariani Foundation, and Telethon Foundation Italy outside the submitted work. N.H. reports grants from the Japan Agency for Medical Research and Development (AMED), –the Japan Society for the Promotion of Science (JSPS), and the Ministry of Education Culture, Sports, Science and Technology Japan; Grant‐in‐Aid for Scientific Research on Innovative Areas; personal fees and others from Dai‐Nippon Sumitomo Pharma Co., Ltd, Takeda Pharmaceutical Co., Ltd, Kyowa Kirin Co., Ltd, GSK K.K., Nippon Boehringer Ingelheim, Co., Ltd, FP Pharmaceutical Corporation, Eisai Co., Ltd, Kissei Pharmaceutical Company, Nihon Medi‐physics Co., Ltd, Novartis Pharma K.K., Biogen Idec Japan Ltd, AbbVie, and Medtronic, Inc.; others from Boston Scientific Japan; personal fees and others from Astellas Pharma Inc.; grants and others from Ono Pharmaceutical Co., Ltd; others from Nihon Pharmaceutical Co., Ltd, Asahi Kasei Medical Co., Ltd, and Mitsubishi Tanabe Pharma Corporation; personal fees and others from Daiichi Sankyo Co.; others from OHARA Pharmaceutical Co., Ltd, and Meiji Seika Pharma; personal fees from Sanofi K.K., Pfizer Japan Inc., Alexion Pharmaceuticals, Mylan N.V., MSD K.K., Lund B
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0885-3185
1531-8257
1531-8257
DOI:10.1002/mds.28902