Association of Body Mass Index and Parkinson Disease: A Bidirectional Mendelian Randomization Study

Cloé Domenighetti¹, Pierre-Emmanuel Sugier¹, Ashwin Ashok Kumar Sreelatha¹, Claudia Schulte¹, Sandeep Grover¹, Berta Portugal¹, Pei-Chen Lee¹, Patrick May¹, Dheeraj Bobbili¹, Milena Radivojkov Blagojevic¹, Peter Lichtner¹, Andrew B Singleton¹, Dena Hernandez¹, Connor Edsall¹, George D Mellick¹, Alexander A Zimprich¹, Walter Pirker¹, Ekaterina A Rogaeva¹, Anthony E Lang¹, Sulev Koks¹, Pille Taba¹, Suzanne Lesage¹, Alexis Brice¹, Jean-Christophe Corvol¹, Marie-Christine Chartier-Harlin¹, Eugenie Mutez¹, Kathrin Brockmann¹, Angela B Deutschlander¹, Georgios M Hadjigeorgiou¹, Efthimios Dardiotis¹, Leonidas Stefanis¹, Athina Maria Simitsi¹, Enza Maria Valente¹, Simona Petrucci¹, Letizia Straniero¹, Anna L Zecchinelli¹, Gianni Pezzoli¹, Laura Brighina¹, Carlo Ferrarese¹, Grazia Annesi¹, Andrea Quattrone¹, Monica Gagliardi¹, Hirotaka Matsuo¹, Akiyoshi Nakayama¹, Nobutaka Hattori¹, Kenya Nishioka¹, Sun Ju Chung¹, Yun Joong Kim¹, Pierre Kolber¹, Bart P C Van De Warrenburg¹, Bastiaan R Bloem¹, Mathias Toft¹, Lasse Pihlstrøm¹, Leonor Correia Guedes¹, Joaquim J Ferreira¹, Soraya Bardien¹, Jonathan Carr¹, Eduardo Tolosa¹, Mario Ezquerra¹, Pau Pastor¹, Monica Diez-Fairen¹, Karin Wirdefeldt¹, Nancy L Pedersen¹, Caroline Ran¹, Andrea C Belin¹, Andreas Puschmann¹, Clara Hellberg¹, Carl E Clarke¹, Karen E Morrison¹, Manuela M Tan¹, Dimitri Krainc¹, Lena F Burbulla¹, Matthew Farrer¹, Rejko Kruger¹, Thomas Gasser¹, Manu Sharma¹, Alexis Elbaz¹; Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (COURAGE-PD) Consortium¹

Affiliations

Affiliation

¹ From the Université Paris-Saclay (C.D., P.-E.S., B.P., A.E.), UVSQ, Inserm, Gustave Roussy, CESP, Villejuif, France; Centre for Genetic Epidemiology (A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, and Department for Neurodegenerative Diseases (C.S., K.B., T.G.), Hertie Institute for Clinical Brain Research, University of Tubingen; German Center for Neurodegenerative Diseases (DZNE) (C.S., K.B., T.G.), Tubingen; Center for Human Genetics (S.G.), Universitatsklinikum Giessen und Marburg, Germany; Department of Public Health (P.-C.L.), National Cheng Kung University, Tainan, Taiwan; Translational Neuroscience (P.M., D.B., R.K.), Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-Belval; Institute of Human Genetics (M.R.B., P.L.), Helmholtz Zentrum München, Neuherberg, Germany; Molecular Genetics Section (A.B.S., D.H., C.E.), Laboratory of Neurogenetics, and Center for Alzheimer's and Related Dementias (A.B.S.), NIA, NIH, Bethesda, MD; Griffith Institute for Drug Discovery (G.D.M.), Griffith University, Nathan, Australia; Department of Neurology (A.A.Z.), Medical University of Vienna; Department of Neurology (W.P.), Wilhelminenspital, Austria; Tanz Centre for Research in Neurodegenerative Diseases (E.A.R., A.E.L.), University of Toronto; Edmond J. Safra Program in Parkinson's Disease (A.E.L.), Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN; Division of Neurology (A.E.L.), University of Toronto; Krembil Brain Institute (A.E.L.), Toronto, Ontario, Canada; Centre for Molecular Medicine and Innovative Therapeutics (S.K.), Murdoch University; Perron Institute for Neurological and Translational Science (S.K.), Nedlands, Australia; Department of Neurology and Neurosurgery (P.T.), University of Tartu; Neurology Clinic (P.T.), Tartu University Hospital, Estonia; Department of Neurologie (S.L., A.B., J.-C.C.), Institut du Cerveau-Paris Brain Institute-ICM, INSERM, CNRS, Assistance Publique Hôpitaux de Paris, Sorbonne Université; Assistance Publique Hôpitaux de Paris (J.-C.C.), Department of Neurology, CIC Neurosciences; Univ. Lille (M.-C.C.-H., E.M.), Inserm, CHU Lille, UMR-S 1172-LilNCog-Centre de Recherche Lille Neurosciences & Cognition, France; Department of Neurology (A.B.D.), Ludwig Maximilians University of Munich; Department of Neurology (A.B.D.), Max Planck Institute of Psychiatry, Munich, Germany; Department of Neurology and Department of Clinical Genomics (A.B.D.), Mayo Clinic Florida, Jacksonville; Department of Neurology (G.M.H., E.D.), Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, Greece; Department of Neurology (G.M.H.), Medical School, University of Cyprus, Nicosia; 1st Department of Neurology (L. Stefanis, A.M.S.), Eginition Hospital, Medical School, National and Kapodistrian University of Athens; Center of Clinical Research, Experimental Surgery and Translational Research (L. Stefanis), Biomedical Research Foundation of the Academy of Athens, Greece; Department of Molecular Medicine (E.M.V.), University of Pavia; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Mondino Foundation (E.M.V.), Pavia; UOC Medical Genetics and Advanced Cell Diagnostics (S.P.), S. Andrea University Hospital, Rome; Department of Clinical and Molecular Medicine (S.P.), University of Rome; Department of Biomedical Sciences (L. Straniero), Humanitas University, Milan; Parkinson Institute (A.L.Z.), Azienda Socio Sanitaria Territoriale (ASST) Gaetano Pini/CTO, Milano; Parkinson Institute (G.P.), Fontazione Grigioni-Via Zuretti, Milan; Department of Neurology (L.B., C.F.), San Gerardo Hospital, Monza; Department of Medicine and Surgery and Milan Center for Neuroscience (L.B., C.F.), University of Milano Bicocca, Milano; Institute for Biomedical Research and Innovation (G.A.), National Research Council, Cosenza; Institute of Neurology (A.Q.), Magna Graecia University; Institute of Molecular Bioimaging and Physiology National Research Council (M.G.), Catanzaro, Italy; Department of Integrative Physiology and Bio-Nano Medicine (H.M., A.N.), National Defense Medical College, Saitama; Department of Neurology (N.H., K.N.), Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan; Department of Neurology (S.J.C.), Asan Medical Center, University of Ulsan College of Medicine; Department of Neurology (Y.J.K.), Yonsei University College of Medicine, Seoul, South Korea; Neurology (P.K., R.K.), Centre Hospitalier de Luxembourg; Department of Neurology (B.P.C.V.D.W., B.R.B.), Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Radboud University Medical Centre, the Netherlands; Department of Neurology (M.T., L.P.), Oslo University Hospital, Norway; Instituto de Medicina Molecular João Lobo Antunes (L.C.G., J.J.F.), Faculdade de Medicina, Universidade de Lisboa; Department of Neurosciences and Mental Health (L.C.G.), Neurology, Hospital de Santa Maria, Centro Hospitalar Universitario Lisboa Norte (CHULN); Laboratory of Clinical Pharmacology and Therapeutics (J.J.F.), Faculdade de Medicina, Universidade de Lisboa, Portugal; Division of Molecular Biology and Human Genetics (S.B.), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa; Division of Neurology (J.C.), Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa; Parkinson's disease & Movement Disorders Unit (E.T.), Neurology Service, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED: CB06/05/0018-ISCIII) (E.T.); Lab of Parkinson Disease and Other Neurodegenerative Movement Disorders (M.E.), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Institut de Neurociències, Universitat de Barcelona; Fundació per la Recerca Biomèdica i Social Mútua Terrassa (P.P., M.D.-F.), Terrassa; Movement Disorders Unit (P.P., M.D.-F.), Department of Neurology, Hospital Universitari Mutua de Terrassa, Barcelona, Spain; Department of Clinical Neuroscience (K.W.), Department of Medical Epidemiology and Biostatistics (K.W., N.L.P.), and Department of Neuroscience (C.R., A.C.B.), Karolinska Institutet, Stockholm; Department of Clinical Sciences Lund (A.P., C.H.), Neurology, Skåne University Hospital, Lund University, Sweden; University of Birmingham and Sandwell and West Birmingham Hospitals NHS Trust (C.E.C.); Faculty of Medicine (K.E.M.), Health and Life Sciences, Queens University, Belfast; Department of Clinical and Movement Neurosciences (M.M.T.), UCL Queen Square Institute of Neurology, University College London, United Kingdom; Department of Neurology (D.K., L.F.B.), Northwestern University Feinberg School of Medicine, Chicago, IL; Metabolic Biochemistry (L.F.B.), Biomedical Center (BMC), Faculty of Medicine, Ludwig-Maximilians-Universität München; Munich Cluster for Systems Neurology (SyNergy) (L.F.B.); German Center for Neurodegenerative Diseases (DZNE) (L.F.B.), Munich, Germany; Department of Neurology (M.F.), McKnight Brain Institute, University of Florida, Gainesville; Parkinson's Research Clinic (R.K.), Centre Hospitalier de Luxembourg; and Transversal Translational Medicine (R.K.), Luxembourg Institute of Health (LIH), Strassen.

PMID: 38986057
PMCID: PMC11759940
DOI: 10.1212/WNL.0000000000209620

Association of Body Mass Index and Parkinson Disease: A Bidirectional Mendelian Randomization Study

Cloé Domenighetti et al. Neurology. 2024.

. 2024 Aug 13;103(3):e209620.

doi: 10.1212/WNL.0000000000209620. Epub 2024 Jul 10.

Authors

Affiliation

¹ From the Université Paris-Saclay (C.D., P.-E.S., B.P., A.E.), UVSQ, Inserm, Gustave Roussy, CESP, Villejuif, France; Centre for Genetic Epidemiology (A.A.K.S., M.S.), Institute for Clinical Epidemiology and Applied Biometry, and Department for Neurodegenerative Diseases (C.S., K.B., T.G.), Hertie Institute for Clinical Brain Research, University of Tubingen; German Center for Neurodegenerative Diseases (DZNE) (C.S., K.B., T.G.), Tubingen; Center for Human Genetics (S.G.), Universitatsklinikum Giessen und Marburg, Germany; Department of Public Health (P.-C.L.), National Cheng Kung University, Tainan, Taiwan; Translational Neuroscience (P.M., D.B., R.K.), Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-Belval; Institute of Human Genetics (M.R.B., P.L.), Helmholtz Zentrum München, Neuherberg, Germany; Molecular Genetics Section (A.B.S., D.H., C.E.), Laboratory of Neurogenetics, and Center for Alzheimer's and Related Dementias (A.B.S.), NIA, NIH, Bethesda, MD; Griffith Institute for Drug Discovery (G.D.M.), Griffith University, Nathan, Australia; Department of Neurology (A.A.Z.), Medical University of Vienna; Department of Neurology (W.P.), Wilhelminenspital, Austria; Tanz Centre for Research in Neurodegenerative Diseases (E.A.R., A.E.L.), University of Toronto; Edmond J. Safra Program in Parkinson's Disease (A.E.L.), Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN; Division of Neurology (A.E.L.), University of Toronto; Krembil Brain Institute (A.E.L.), Toronto, Ontario, Canada; Centre for Molecular Medicine and Innovative Therapeutics (S.K.), Murdoch University; Perron Institute for Neurological and Translational Science (S.K.), Nedlands, Australia; Department of Neurology and Neurosurgery (P.T.), University of Tartu; Neurology Clinic (P.T.), Tartu University Hospital, Estonia; Department of Neurologie (S.L., A.B., J.-C.C.), Institut du Cerveau-Paris Brain Institute-ICM, INSERM, CNRS, Assistance Publique Hôpitaux de Paris, Sorbonne Université; Assistance Publique Hôpitaux de Paris (J.-C.C.), Department of Neurology, CIC Neurosciences; Univ. Lille (M.-C.C.-H., E.M.), Inserm, CHU Lille, UMR-S 1172-LilNCog-Centre de Recherche Lille Neurosciences & Cognition, France; Department of Neurology (A.B.D.), Ludwig Maximilians University of Munich; Department of Neurology (A.B.D.), Max Planck Institute of Psychiatry, Munich, Germany; Department of Neurology and Department of Clinical Genomics (A.B.D.), Mayo Clinic Florida, Jacksonville; Department of Neurology (G.M.H., E.D.), Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, Greece; Department of Neurology (G.M.H.), Medical School, University of Cyprus, Nicosia; 1st Department of Neurology (L. Stefanis, A.M.S.), Eginition Hospital, Medical School, National and Kapodistrian University of Athens; Center of Clinical Research, Experimental Surgery and Translational Research (L. Stefanis), Biomedical Research Foundation of the Academy of Athens, Greece; Department of Molecular Medicine (E.M.V.), University of Pavia; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Mondino Foundation (E.M.V.), Pavia; UOC Medical Genetics and Advanced Cell Diagnostics (S.P.), S. Andrea University Hospital, Rome; Department of Clinical and Molecular Medicine (S.P.), University of Rome; Department of Biomedical Sciences (L. Straniero), Humanitas University, Milan; Parkinson Institute (A.L.Z.), Azienda Socio Sanitaria Territoriale (ASST) Gaetano Pini/CTO, Milano; Parkinson Institute (G.P.), Fontazione Grigioni-Via Zuretti, Milan; Department of Neurology (L.B., C.F.), San Gerardo Hospital, Monza; Department of Medicine and Surgery and Milan Center for Neuroscience (L.B., C.F.), University of Milano Bicocca, Milano; Institute for Biomedical Research and Innovation (G.A.), National Research Council, Cosenza; Institute of Neurology (A.Q.), Magna Graecia University; Institute of Molecular Bioimaging and Physiology National Research Council (M.G.), Catanzaro, Italy; Department of Integrative Physiology and Bio-Nano Medicine (H.M., A.N.), National Defense Medical College, Saitama; Department of Neurology (N.H., K.N.), Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan; Department of Neurology (S.J.C.), Asan Medical Center, University of Ulsan College of Medicine; Department of Neurology (Y.J.K.), Yonsei University College of Medicine, Seoul, South Korea; Neurology (P.K., R.K.), Centre Hospitalier de Luxembourg; Department of Neurology (B.P.C.V.D.W., B.R.B.), Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Radboud University Medical Centre, the Netherlands; Department of Neurology (M.T., L.P.), Oslo University Hospital, Norway; Instituto de Medicina Molecular João Lobo Antunes (L.C.G., J.J.F.), Faculdade de Medicina, Universidade de Lisboa; Department of Neurosciences and Mental Health (L.C.G.), Neurology, Hospital de Santa Maria, Centro Hospitalar Universitario Lisboa Norte (CHULN); Laboratory of Clinical Pharmacology and Therapeutics (J.J.F.), Faculdade de Medicina, Universidade de Lisboa, Portugal; Division of Molecular Biology and Human Genetics (S.B.), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa; Division of Neurology (J.C.), Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa; Parkinson's disease & Movement Disorders Unit (E.T.), Neurology Service, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED: CB06/05/0018-ISCIII) (E.T.); Lab of Parkinson Disease and Other Neurodegenerative Movement Disorders (M.E.), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Institut de Neurociències, Universitat de Barcelona; Fundació per la Recerca Biomèdica i Social Mútua Terrassa (P.P., M.D.-F.), Terrassa; Movement Disorders Unit (P.P., M.D.-F.), Department of Neurology, Hospital Universitari Mutua de Terrassa, Barcelona, Spain; Department of Clinical Neuroscience (K.W.), Department of Medical Epidemiology and Biostatistics (K.W., N.L.P.), and Department of Neuroscience (C.R., A.C.B.), Karolinska Institutet, Stockholm; Department of Clinical Sciences Lund (A.P., C.H.), Neurology, Skåne University Hospital, Lund University, Sweden; University of Birmingham and Sandwell and West Birmingham Hospitals NHS Trust (C.E.C.); Faculty of Medicine (K.E.M.), Health and Life Sciences, Queens University, Belfast; Department of Clinical and Movement Neurosciences (M.M.T.), UCL Queen Square Institute of Neurology, University College London, United Kingdom; Department of Neurology (D.K., L.F.B.), Northwestern University Feinberg School of Medicine, Chicago, IL; Metabolic Biochemistry (L.F.B.), Biomedical Center (BMC), Faculty of Medicine, Ludwig-Maximilians-Universität München; Munich Cluster for Systems Neurology (SyNergy) (L.F.B.); German Center for Neurodegenerative Diseases (DZNE) (L.F.B.), Munich, Germany; Department of Neurology (M.F.), McKnight Brain Institute, University of Florida, Gainesville; Parkinson's Research Clinic (R.K.), Centre Hospitalier de Luxembourg; and Transversal Translational Medicine (R.K.), Luxembourg Institute of Health (LIH), Strassen.

PMID: 38986057
PMCID: PMC11759940
DOI: 10.1212/WNL.0000000000209620

Abstract

Background and objectives: The role of body mass index (BMI) in Parkinson disease (PD) is unclear. Based on the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in PD (Courage-PD) consortium, we used 2-sample Mendelian randomization (MR) to replicate a previously reported inverse association of genetically predicted BMI with PD and investigated whether findings were robust in analyses addressing the potential for survival and incidence-prevalence biases. We also examined whether the BMI-PD relation is bidirectional by performing a reverse MR.

Methods: We used summary statistics from a genome-wide association study (GWAS) to extract the association of 501 single-nucleotide polymorphisms (SNPs) with BMI and from the Courage-PD and international Parkinson Disease Genomics Consortium (iPDGC) to estimate their association with PD. Analyses are based on participants of European ancestry. We used the inverse-weighted method to compute odds ratios (OR_IVW per 4.8 kg/m² [95% CI]) of PD and additional pleiotropy robust methods. We performed analyses stratified by age, disease duration, and sex. For reverse MR, we used SNPs associated with PD from 2 iPDGC GWAS to assess the effect of genetic liability toward PD on BMI.

Results: Summary statistics for BMI are based on 806,834 participants (54% women). Summary statistics for PD are based on 8,919 (40% women) cases and 7,600 (55% women) controls from Courage-PD, and 19,438 (38% women) cases and 24,388 (51% women) controls from iPDGC. In Courage-PD, we found an inverse association between genetically predicted BMI and PD (OR_IVW 0.82 [0.70-0.97], p = 0.012) without evidence for pleiotropy. This association tended to be stronger in younger participants (≤67 years, OR_IVW 0.71 [0.55-0.92]) and cases with shorter disease duration (≤7 years, OR_IVW 0.75 [0.62-0.91]). In pooled Courage-PD + iPDGC analyses, the association was stronger in women (OR_IVW 0.85 [0.74-0.99], p = 0.032) than men (OR_IVW 0.92 [0.80-1.04], p = 0.18), but the interaction was not statistically significant (p-interaction = 0.48). In reverse MR, there was evidence for pleiotropy, but pleiotropy robust methods showed a significant inverse association.

Discussion: Using an independent data set (Courage-PD), we replicate an inverse association of genetically predicted BMI with PD, not explained by survival or incidence-prevalence biases. Moreover, reverse MR analyses support an inverse association between genetic liability toward PD and BMI, in favor of a bidirectional relation.

PubMed Disclaimer

Conflict of interest statement

C. Domenighetti has received a doctoral grant from Université Paris-Saclay, France. P. May has received funding from the Fonds National de Recherche (FNR), Luxembourg, as part of the National Centre of Excellence in Research on Parkinson's Disease (NCER-PD, FNR11264123), the DFG Research Units FOR2715 (INTER/DFG/17/11583046), and FOR2488 (INTER/DFG/19/14429377). A.B. Singleton has received funding from the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services, project ZO1 AG000949, has received grants from the Department of Defense during the conduct of the study, has received grants from the Michael J. Fox Foundation outside the submitted work, and is an unpaid Scientific Advisory Board member for Cajal Neuroscience outside of the submitted work. D.G. Hernandez and C. Edsall have received funding from the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services, project ZO1 AG000949. W. Pirker has received personal fees from Grünenthal, AbbVie, AOP Health Orphan, Zambon, Boehringer Ingelheim, Stada, and Bial UCB Pharma. E. Rogaeva has received funding from the Canadian Consortium on Neurodegeneration in Aging. A.E. Lang has received personal fees from AbbVie, AFFiRis, Janssen, Biogen, Merck, Sun Pharma, Corticobasal Solutions, Sunovion, Paladin, Lilly, Medtronic, Theravance, Lundbeck, Retrophin, Roche, PhotoPharmics. S. Koks has received funding from MSWA. P. Taba has received Estonian Research Council Grant PRG957. A. Brice has received grants from France Parkinson, FRC, ANR—EPIG—Agence nationale de recherche, ANR—JPND—Agence nationale de recherche, RDS (Roger de Spoelberch Foundation), France Alzheimer, and Institut de France, ANR—EPIG, FMR (maladies rares). J.C. Corvol has received grants from the Michael J. Fox Foundation and Sanofi, and has served on advisory boards for Air Liquide, Biogen, Denali, Ever Pharma, Idorsia, Prevail Therapeutic, Theranexus, and UCB, outside the submitted work. K. Brockmann has received research funding from the Michael J. Fox Foundation for Parkinson's Research (MJFF-022343, MJFF-023275, MJFF-023365), the German Society for Parkinson DPG, the Health Forum Baden Wuerttemberg, the Else Kröner Fresenius Stiftung (ClinbrAIn), the University of Tuebingen, and the German Research Foundation DFG (BR-655671-1). K. Brockmann is a consultant for F. Hoffmann-La Roche Ltd., Vanqua Bio, and the Michael J. Fox Foundation for Parkinson's Research, and has received speaker honoraria from Abbvie, Lundbeck, UCB, and Zambon. L. Stefanis 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 number 778003), «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), is co-Head and PI at the NKUA of the General Secretariat of Research and Technology (GSRT)-funded Grant “National Network of Precision Medicine for Neurodegenerative Diseases,” has served on an Advisory Board for Abbvie, ITF Hellas, and Biogen and has received honoraria from Abbvie and Sanofi. E.M. Valente serves as an associate editor of Journal of Medical Genetics, serves as a section editor of Pediatric Research, is a member of the editorial board of Movement Disorders Clinical Practice; grants from the Italian Ministry of Health (Ricerca Corrente 2021), the CARIPLO Foundation, the Pierfranco and Luisa Mariani Foundation, and Telethon Foundation Italy. N. Hattori reports grants from the Japan Agency for Medical Research and Development (AMED), 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, Ono Pharmaceutical Co. Ltd., Nihon Pharmaceutical Co. Ltd., Asahi Kasei Medical Co. Ltd., and the Mitsubishi Tanabe Pharma Corporation, and has received personal fees 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, Medtronic, Inc., Boston Scientific Japan, Astellas Pharma Inc., Daiichi Sankyo Co. OHARA Pharmaceutical Co. Ltd., Meiji Seika Pharma, Sanofi K.K., Pfizer Japan Inc., Alexion Pharmaceuticals, Mylan N.V., MSD K.K., LundBeck Japan, and Hisamitsu Pharmaceutical Co. Inc., outside the submitted work. K. Nishioka has received grants from the Japan Society for the Promotion of Science (JSPS). P. Kolber has received funding from Centre Hospitalier de Luxembourg, the University of Luxembourg, and has received grants from Fonds National de Recherche (FNR). B.P.C. van de Warrenburg has received grants from ZonMw, Hersenstichting, Gossweiler Fund, Radboud University Medical Centre, and the Christina Foundation, has received consulting fees from Biohaven Pharmaceuticals, Vico Therapeutics, and Servier, and receives royalties from BSL/Springer-Nature. B.R. Bloem has received grants from the Netherlands Organization for Health Research and Development, the Michael J. Fox Foundation, Parkinson Vereniging, the Parkinson Foundation, the Gatsby Foundation, Verily Life Sciences, Horizon 2020, Topsector Life Sciences and Health, Stichting Parkinson Fonds, UCB, and Abbvie, has received personal fees from Biogen, Abbvie, Walk with Path, UCB, Abbvie, Zambon, Bial, and Roche, serves as editor-in-chief of the Journal of Parkinson's Disease, and serves on the editorial board of Practical Neurology and Digital Biomarkers. M. Toft has received grants from the Research Council of Norway during the conduct of the study; grants from the South-Eastern Norway Regional Health Authority, and the Michael J. Fox Foundation. L. Pihlstrøm has received grants from the Norwegian Health Association and the South-Eastern Norway Regional Health Authority. J.J. Ferreira has received 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 has received personal fees from Faculdade de Medicina de Lisboa, CNS—Campus Neurológico Sénior, BIAL, and Novartis. S. Bardien and J. Carr have received funding from grants from the National Research Foundation of South Africa (106052, 129249); the South African Medical Research Council (Self-Initiated Research Grant); and Stellenbosch University, South Africa; and have received funding from the NRF-DST Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research; and the Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town. E. Tolosa has received consulting honoraria from TEVA, Bial, Prevail Therapeutics, Boehringer Ingelheim, Roche, and BIOGEN, and has received research funding 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). P. Pastor and M. Diez-Fairen have received funding from the Spanish Ministry of Science and Innovation (SAF2013-47939-R). K. Wirdefeldt and N.L. Pedersen have received funding from the Swedish Research Council (K2002-27X-14056-02B, 521-2010-2479, 521-2013-2488, 2017-02175). N.L. Pedersen has also received funding from the National Institutes of Health (ES10758 and AG 08724). C. Ran has received funding from the Märta Lundkvist Foundation, the Swedish Brain Foundation, and Karolinska Institutet Research Funds. A.C. Belin has received funding from the Swedish Brain Foundation, the Swedish Research Council, and Karolinska Institutet Research Funds. A. Puschmann reports grants from Parkinsonfonden (The Swedish Parkinson Foundation), ALF (Swedish Government), Region Skåne, Sweden, Skåne University Hospital, Hans-Gabriel och Trolle Wachtmeister Stiftelse för Medicinsk Forskning, Sweden, Multipark, and has received personal fees from Elsevier. M. Tan has received grants from Parkinson's UK, the Michael J. Fox Foundation, and has received funding from University College London. R. Kruger has received grants from Fonds National de Recherche Luxembourg (FNR), German Research Council (DFG), has received non-financial support from Abbvie, Zambon, Luxembourg/German Research Council (DFG), and Fonds National de Recherche, Luxembourg (FNR), and has received personal fees from the University of Luxembourg, the Luxembourg Institute of Health, Centre Hospitalier de Luxembourg, Desitin/Zambon, Abbvie GmbH, and Medtronic GmbH. T. Gasser has received personal fees from UCB Pharma, Novartis, TEVA, and MedUpdate, and has received grants from the Michael J. Fox Foundation for Parkinson's Research, Bundesministerium für Bildung und Forschung (BMBF), Deutsche Forschungsgemeinschaft (DFG), and the “Joint Programming for Neurodegenerative Diseases” (JPND) program, funded by the European Commission, outside the submitted work, in addition, Dr. Gasser has Patent Number: EP1802749 (A2) KASPP (LRRK2) gene (its production and use for the detection and treatment of neurodegenerative disorders issued). M. Sharma has received grants from the German Research Council (DFG/SH 599/6-1), the MSA Coalition, and the Michael J. Fox Foundation (USA Genetic Diversity in PD Program: GAP-India Grant ID: 17473). A. Elbaz has received grants from Agence nationale de la recherche (ANR), the Michael J. Fox Foundation, Plan Ecophyto (French ministry of agriculture), and France Parkinson. All other authors report no relevant disclosures. Go to Neurology.org/N for full disclosures.

Figures

**Figure 1. Mendelian Randomization Estimates for Association Between BMI and PD, Overall and After Stratification by Age at Study, Disease Duration, and Sex**
BMI = body mass index; iPDGC = international Parkinson Disease Genomics Consortium; OR = odds ratio per 4.8 kg/m²; PD = Parkinson disease.

**Figure 2. Mendelian Randomization Estimates for Association Between BMI and PD After Excluding SNPs Associated With Traits Related to PD**
BMI = body mass index; HDL = high-density lipoprotein; LDL = low-density lipoprotein; OR = odds ratio per 4.8 kg/m²; PD = Parkinson disease; SNP = single-nucleotide polymorphism.

See this image and copyright information in PMC

References

1. Wang YL, Wang YT, Li JF, Zhang YZ, Yin HL, Han B. Body mass index and risk of Parkinson's disease: a dose-response meta-analysis of prospective studies. PLoS One. 2015;10(6):e0131778. doi: 10.1371/journal.pone.0131778 - DOI - PMC - PubMed
1. Rahmani J, Roudsari AH, Bawadi H, et al. Body mass index and risk of Parkinson, Alzheimer, Dementia, and Dementia mortality: a systematic review and dose-response meta-analysis of cohort studies among 5 million participants. Nutr Neurosci. 2022;25(3):423-431. doi: 10.1080/1028415X.2020.1758888 - DOI - PubMed
1. Savica R, Boeve BF, Mielke MM. When do α-synucleinopathies start? An epidemiological timeline: a review. JAMA Neurol. 2018;75(4):503-509. doi: 10.1001/jamaneurol.2017.4243 - DOI - PubMed
1. Chen H, Zhang SM, Hernán MA, Willett WC, Ascherio A. Weight loss in Parkinson's disease. Ann Neurol. 2003;53(5):676-679. doi: 10.1002/ana.10577 - DOI - PubMed
1. Song S, Luo Z, Li C, et al. Changes in body composition before and after Parkinson's disease diagnosis. Mov Disord. 2021;36(7):1617-1623. doi: 10.1002/mds.28536 - DOI - PMC - PubMed

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
Medical
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Association of Body Mass Index and Parkinson Disease: A Bidirectional Mendelian Randomization Study

Affiliation

Association of Body Mass Index and Parkinson Disease: A Bidirectional Mendelian Randomization Study

Authors

Affiliation

Abstract

Conflict of interest statement

Figures

References

MeSH terms

LinkOut - more resources

Full Text Sources

Medical