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

Cloé Domenighetti¹, Pierre-Emmanuel Sugier¹, Ashwin Ashok Kumar Sreelatha², Claudia Schulte^{3

4}, Sandeep Grover², Océane Mohamed¹, Berta Portugal¹, Patrick May⁵, Dheeraj R Bobbili⁵, Milena Radivojkov-Blagojevic⁶, Peter Lichtner⁶, Andrew B Singleton^{7

8}, Dena G Hernandez⁷, Connor Edsall⁷, George D Mellick⁹, Alexander Zimprich¹⁰, Walter Pirker¹¹, Ekaterina Rogaeva¹², Anthony E Lang^{12

13

14

15}, Sulev Koks^{16

17}, Pille Taba^{18

19}, Suzanne Lesage²⁰, Alexis Brice²⁰, Jean-Christophe Corvol^{20

21}, Marie-Christine Chartier-Harlin²², Eugénie Mutez²², Kathrin Brockmann^{3

4}, Angela B Deutschländer^{23

24

25}, Georges M Hadjigeorgiou^{26

27}, Efthimos Dardiotis²⁶, Leonidas Stefanis^{28

29}, Athina Maria Simitsi²⁸, Enza Maria Valente^{30

31}, Simona Petrucci^{32

33}, Stefano Duga^{34

35}, Letizia Straniero³⁴, Anna Zecchinelli³⁶, Gianni Pezzoli³⁷, Laura Brighina^{38

39}, Carlo Ferrarese^{38

39}, Grazia Annesi⁴⁰, Andrea Quattrone⁴¹, Monica Gagliardi⁴², Hirotaka Matsuo⁴³, Yusuke Kawamura⁴³, Nobutaka Hattori⁴⁴, Kenya Nishioka⁴⁴, Sun Ju Chung⁴⁵, Yun Joong Kim⁴⁶, Pierre Kolber⁴⁷, Bart P C van de Warrenburg⁴⁸, Bastiaan R Bloem⁴⁸, Jan Aasly⁴⁹, Mathias Toft⁵⁰, Lasse Pihlstrøm⁵⁰, Leonor Correia Guedes^{51

52}, Joaquim J Ferreira^{51

53}, Soraya Bardien⁵⁴, Jonathan Carr⁵⁵, Eduardo Tolosa^{56

57}, Mario Ezquerra⁵⁸, Pau Pastor^{59

60}, Monica Diez-Fairen^{59

60}, Karin Wirdefeldt^{61

62}, Nancy L Pedersen⁶², Caroline Ran⁶³, Andrea C Belin⁶³, Andreas Puschmann⁶⁴, Clara Hellberg⁶⁴, Carl E Clarke⁶⁵, Karen E Morrison⁶⁶, Manuela Tan⁶⁷, Dimitri Krainc⁶⁸, Lena F Burbulla^{68

69

70

71}, Matt J Farrer⁷², Rejko Krüger^{5

47

73

74}, Thomas Gasser^{3

4}, Manu Sharma², Alexis Elbaz¹; Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (Courage-PD) Consortium

Affiliations

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

PMID: 34997937
DOI: 10.1002/mds.28902

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

Cloé Domenighetti et al. Mov Disord. 2022 Apr.

. 2022 Apr;37(4):857-864.

doi: 10.1002/mds.28902. Epub 2022 Jan 8.

Authors

Affiliations

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

PMID: 34997937
DOI: 10.1002/mds.28902

Abstract

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.

Keywords: dairy intake; Parkinson's disease; Mendelian randomization.

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References

1. Jiang W, Ju C, Jiang H, Zhang D. Dairy foods intake and risk of Parkinson's disease: a dose-response meta-analysis of prospective cohort studies. Eur J Epidemiol 2014;29:613-619.
1. Elbaz A. Prodromal symptoms of Parkinson's disease: implications for epidemiological studies of disease etiology. Rev Neurol (Paris) 2016;172:503-511.
1. Burgess S, Davey Smith G, Davies NM, et al. Guidelines for performing Mendelian randomization investigations. Wellcome Open Res 2019;4:186.
1. Mendelian Randomization of Dairy Consumption Working Group. Dairy consumption and body mass index among adults: Mendelian randomization analysis of 184802 individuals from 25 studies. Clin Chem 2018;64:183-191.
1. Mendelian Randomization of Dairy Consumption Working Group. Dairy intake and body composition and Cardiometabolic traits among adults: Mendelian randomization analysis of 182041 individuals from 18 studies. Clin Chem 2019;65:751-760.

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

Affiliations

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

Authors

Affiliations

Abstract

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources