The Lancet. NeurologyReview
undefined Dec 2024
Knowledge on the genetic basis of Parkinson's disease has grown tremendously since the discovery of the first monogenic form, caused by a mutation in α-synuclein, and with the subsequent identification of multiple other causative genes and associated loci.
Genetic studies provide insights into the phenotypic heterogeneity and global distribution of Parkinson's disease. By shedding light on the underlying biological mechanisms, genetics facilitates the identification of new biomarkers and therapeutic targets.
Several clinical trials of genetics-informed therapies are ongoing or imminent. International programmes in populations who have been under-represented in Parkinson's disease genetics research are fostering collaboration and capacity-building, and have already generated novel findings.
Many challenges remain for genetics research in these populations, but addressing them provides opportunities to obtain a more complete and equitable understanding of Parkinson's disease globally.
These advances facilitate the integration of genetics into the clinic, to improve patient management and personalised medicine.
Declaration of interests SYL is an employee at the University of Malaya. SYL has received stipends from the International Parkinson and Movement Disorder Society (MDS) as Chair of the Asian-Oceanian Section, and Science Advances as Associate Editor (Neuroscience). He reports consultancies from the Michael J Fox Foundation (MJFF), the Aligning Science Across Parkinson's-Global Parkinson's Genetics Program (ASAP-GP2), and Neurotorium Editorial Board; honoraria for lecturing from the MDS, Lundbeck, Eisai, and Medtronic; and research grants from the Malaysian Ministry of Education Fundamental Research Grant Scheme and the MJFF. AHT is an employee at the University of Malaya. AHT has received grants from and served as a consultant for the MJFF and the ASAP-GP2. AHT has received honoraria for lecturing from the MDS and Boehringer Ingelheim. NUO is employed by the College of Medicine, University of Lagos and receives institutional research grant support from the ASAP-GP2, the MJFF, and the UK National Institute for Health and Care Research for Parkinson's disease research including Parkinson's disease genetics studies. NUO has received honoraria as speaker from the MDS. HRM is employed by University College London. HRM reports paid consultancy from Roche, Aprinoia, AI Therapeutics, and Amylyx; lecture fees and honoraria from the British Medical Journal, Kyowa Kirin, and the MDS; research grants from Parkinson's UK, the Cure Parkinson's Trust, PSP Association, Medical Research Council, and the MJFF. HRM is a co-applicant on a patent application related to C9ORF72 (method for diagnosing a neurodegenerative disease; PCT/GB2012/052140). IM reports receiving research grants from the National Institutes of Health (1R01NS112499), the MJFF, and the ASAP-GP2. IM is also a member of the MDS-PAS Executive Committee and the PDGENEration Latino Advisory Council from the Parkinson's Foundation and has received honoraria as speaker from the MDS. LML reports receiving support from the Bachmann-Strauss Dystonia & Parkinson Foundation as part of a research fellowship. She also received a travel stipend to attend the Samuel Belzberg Dystonia Symposium in 2023. JNF is an employee at Nanyang Technological University Singapore, and received the National Medical Research Council Open Fund Individual Research Grant (MOH-000559) and the Ministry of Education Academic Research Funds (MOE-T2EP30220-0005 and MOE-MOET32020-0004). ES is employed by the University of Dundee, UK and has received research funding from the MJFF, the Chief Scientist Office in Scotland, and UK Research and Innovation Medical Research Council. AJN is employed by Queen Mary University of London. AJN reports grants from Parkinson's UK, Barts Charity, Cure Parkinson's, National Institute for Health and Care Research, Innovate UK, Solvemed, the Medical College of Saint Bartholomew's Hospital Trust, Alchemab, and the MJFF. AJN reports consultancy and personal fees from AstraZeneca, AbbVie, Profile, Bial, Charco Neurotech, Alchemab, Sosei Heptares, Umedeor, and Britannia, outside the submitted work. AJN has share options in Umedeor. WL reports research grants from the National Natural Science Foundation of China and the Science Technology Department of Zhejiang Province, China. RO has received travel grants from the MDS in 2022 and 2023, and received a research grant in 2022 and travel support to attend the annual GP2 meeting in 2022 and 2023 from ASAP-GP2. ABS is employed by the National Institutes of Health. He has received grants from the MJFF, and is a member of the scientific advisory board of Cajal Neuroscience. CB is a federal employee of the National Institutes of Health (NIH) USA, specifically the National Institute on Aging. He reports receiving research grants from the MJFF and ASAP-GP2. CK is the recipient of research grants from the German Research Foundation, ASAP-GP2, and the MJFF. CK has received travel grants and faculty honoraria from the MDS, and stipends as Deputy Editor of Movement Disorders and Science Advances, as well as a member of the Science Committee of the Else Kroener Fresenius Foundation. CK serves as a medical advisor to Centogene, Takeda, and Retromer Therapeutics, and has received speakers' honoraria from Bial and Desitin. AAA, KL, TST, YWT, SBC, JCEO, and NB declare no competing interests.
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