Mitochondrial haplogroups and cognitive progression in Parkinson's disease

Ganqiang Liu; Chunming Ni; Jiamin Zhan; Weimin Li; Junfeng Luo; Zhixiang Liao; Joseph J Locascio; Wenbiao Xian; Ling Chen; Zhong Pei; Jean-Christophe Corvol; Jodi Maple-Grødem; Meghan C Campbell; Alexis Elbaz; Suzanne Lesage; Alexis Brice; Albert Y Hung; Michael A Schwarzschild; Michael T Hayes; Anne-Marie Wills; Bernard Ravina; Ira Shoulson; Pille Taba; Sulev Kõks; Thomas G Beach; Florence Cormier-Dequaire; Guido Alves; Ole-Bjørn Tysnes; Joel S Perlmutter; Peter Heutink; Jacobus J van Hilten; Roger A Barker; Caroline H Williams-Gray; Clemens R Scherzer; International Genetics of Parkinson Disease Progression (IGPP) Consortium

doi:10.1093/brain/awac327

Mitochondrial haplogroups and cognitive progression in Parkinson's disease

Brain. 2023 Jan 5;146(1):42-49. doi: 10.1093/brain/awac327.

Authors

Ganqiang Liu¹, Chunming Ni¹, Jiamin Zhan¹, Weimin Li¹, Junfeng Luo¹, Zhixiang Liao^{2

3}, Joseph J Locascio^{2

3

4}, Wenbiao Xian⁵, Ling Chen⁵, Zhong Pei⁵, Jean-Christophe Corvol⁶, Jodi Maple-Grødem^{7

8}, Meghan C Campbell⁹, Alexis Elbaz¹⁰, Suzanne Lesage⁶, Alexis Brice⁶, Albert Y Hung⁴, Michael A Schwarzschild⁴, Michael T Hayes¹¹, Anne-Marie Wills⁴, Bernard Ravina¹², Ira Shoulson¹³, Pille Taba^{14

15}, Sulev Kõks^{16

17}, Thomas G Beach¹⁸, Florence Cormier-Dequaire⁶, Guido Alves^{7

8

19}, Ole-Bjørn Tysnes^{20

21}, Joel S Perlmutter^{9

22

23}, Peter Heutink²⁴, Jacobus J van Hilten²⁵, Roger A Barker^{26

27}, Caroline H Williams-Gray²⁶, Clemens R Scherzer^{2

3

4

11}; International Genetics of Parkinson Disease Progression (IGPP) Consortium

Collaborators

International Genetics of Parkinson Disease Progression (IGPP) Consortium:
Ganqiang Liu, Rebecca R Valentino, Jiajie Peng, Zhixiang Liao, Joseph J Locascio, Jean-Christophe Corvol, Xianjun Dong, Jodi Maple-Grødem, Meghan C Campbell, Alexis Elbaz, Suzanne Lesage, Alexis Brice, Graziella Mangone, John H Growdon, Albert Y Hung, Michael A Schwarzchild, Michael T Hayes, Anne-Marie Wills, Todd M Herrington, Bernard Ravian, Ira Shoulson, Pille Taba, Sulev Kõks, Thomas G Beach, Florence Cormier-Dequaire, Guido Alves, Ole-Bjørn Tysnes, Joel S Perlmutter, Peter Heutink, Jacobus J van Hilten, Meike Kasten, Brit Mollenhauer, Claudia Trenkwalder, Christine Klein, Roger A Barker, Caroline H Williams-Gray, Johan Marinus, Clemens R Scherzer

Affiliations

¹ Neurobiology Research Center, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Shenzhen, Guangdong 518107, China.
² APDA Center for Advanced Parkinson Research, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
³ Neurogenomics Lab, Harvard Medical School, Brigham and Women's Hospital, Boston, MA 02115, USA.
⁴ Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
⁵ Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
⁶ Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Assistance Publique Hôpitaux de Paris, Département de Neurologie et de Génétique, Hôpital Pitié-Salpêtrière, F-75013 Paris, France.
⁷ The Norwegian Centre for Movement Disorders, Stavanger University Hospital, 4068 Stavanger, Norway.
⁸ Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, 4021 Stavanger, Norway.
⁹ Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
¹⁰ Paris-Saclay University, UVSQ, Inserm, Gustave Roussy, 'Exposome and Heredity' Team, CESP, F94805 Villejuif, France.
¹¹ Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA.
¹² Praxis Precision Medicines, Cambridge, MA 02142, USA.
¹³ Department of Neurology, Center for Health and Technology, University of Rochester, Rochester, NY 14642, USA.
¹⁴ Department of Neurology and Neurosurgery, Institute of Clinical Medicine, University of Tartu, Tartu 50406, Estonia.
¹⁵ Neurology Clinic, Tartu University Hospital, Tartu 50406, Estonia.
¹⁶ Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Murdoch, Perth, WA 6150, Australia.
¹⁷ Perron Institute for Neurological and Translational Science, Nedlands, WA 6009, Australia.
¹⁸ Banner Sun Health Research Institute, Sun City, AZ 85351, USA.
¹⁹ Department of Neurology, Stavanger University Hospital, 4068 Stavanger, Norway.
²⁰ Department of Neurology, Haukeland University Hospital, 5020 Bergen, Norway.
²¹ Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway.
²² Departments of Radiology and Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA.
²³ Program of Physical Therapy and Program of Occupational Therapy, Washington University School of Medicine, St. Louis, MO 63110, USA.
²⁴ German Center for Neurodegenerative diseases (DZNE), 72076 Tübingen, Germany.
²⁵ Department of Neurology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
²⁶ John Van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0PY, UK.
²⁷ Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK.

Abstract

Mitochondria are a culprit in the onset of Parkinson's disease, but their role during disease progression is unclear. Here we used Cox proportional hazards models to exam the effect of variation in the mitochondrial genome on longitudinal cognitive and motor progression over time in 4064 patients with Parkinson's disease. Mitochondrial macro-haplogroup was associated with reduced risk of cognitive disease progression in the discovery and replication population. In the combined analysis, patients with the super macro-haplogroup J, T, U# had a 41% lower risk of cognitive progression with P = 2.42 × 10-6 compared to those with macro-haplogroup H. Exploratory analysis indicated that the common mitochondrial DNA variant, m.2706A>G, was associated with slower cognitive decline with a hazard ratio of 0.68 (95% confidence interval 0.56-0.81) and P = 2.46 × 10-5. Mitochondrial haplogroups were not appreciably linked to motor progression. This initial genetic survival study of the mitochondrial genome suggests that mitochondrial haplogroups may be associated with the pace of cognitive progression in Parkinson's disease over time.

Keywords: Parkinson’s disease; cognitive progression; mitochondrial haplogroups.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Cognition
DNA, Mitochondrial / genetics
Disease Progression
Haplotypes
Humans
Mitochondria / genetics
Parkinson Disease* / epidemiology
Parkinson Disease* / genetics

Substances

DNA, Mitochondrial

Abstract

Publication types

MeSH terms

Substances

Grants and funding