Evaluation of a Mitochondrial Polygenic Score for Parkinson's Disease Across Ancestries

Joshua Chin Ern Ooi¹, Yi Wen Tay², Ai Huey Tan^{3

4}, Chin-Hsien Lin⁵, Kajsa Atterling Brolin^{6

7}, Björn-Hergen Laabs⁸, Sebastian Sendel⁹, Inke R König⁸, Amke Caliebe⁹, Carolin Gabbert¹⁰, Katherine M Andersh¹¹, Lietsel Jones^{11

12}, Lara M Lange^{10

13}, Brian Fiske¹⁴, Carolyn Sue^{15

16}, Christine Klein¹⁰, Joanne Trinh¹⁰, Theresa Lüth¹⁰; Global Parkinson's Genetics Program (GP2)

Affiliations

¹ Neurology Unit, Queen Elizabeth Hospital, Kota Kinabalu, Malaysia.
² Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
³ Division of Neurology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
⁴ The Mah Pooi Soo & Tan Chin Nam Centre for Parkinson's & Related Disorders, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
⁵ Department of Neurology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
⁶ Translational Neurogenetics Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden.
⁷ Centre for Preventive Neurology, Wolfson Institute of Population Health, Queen Mary University of London, London, UK.
⁸ Institute of Medical Biometry and Statistics, University of Lübeck, Lübeck, Germany.
⁹ Institute of Medical Informatics and Statistics, Kiel University and University Hospital Schleswig-Holstein, Kiel, Germany.
¹⁰ Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
¹¹ Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
¹² DataTecnica LLC, Washington, District of Columbia, USA.
¹³ Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
¹⁴ The Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA.
¹⁵ Neuroscience Research Australia (NeuRA), Randwick, New South Wales, Australia.
¹⁶ Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia.

PMID: 40631485
PMCID: PMC12485575
DOI: 10.1002/mds.30285

Evaluation of a Mitochondrial Polygenic Score for Parkinson's Disease Across Ancestries

Joshua Chin Ern Ooi et al. Mov Disord. 2025 Sep.

. 2025 Sep;40(9):2015-2018.

doi: 10.1002/mds.30285. Epub 2025 Jul 9.

Authors

Affiliations

¹ Neurology Unit, Queen Elizabeth Hospital, Kota Kinabalu, Malaysia.
² Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
³ Division of Neurology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
⁴ The Mah Pooi Soo & Tan Chin Nam Centre for Parkinson's & Related Disorders, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
⁵ Department of Neurology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
⁶ Translational Neurogenetics Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden.
⁷ Centre for Preventive Neurology, Wolfson Institute of Population Health, Queen Mary University of London, London, UK.
⁸ Institute of Medical Biometry and Statistics, University of Lübeck, Lübeck, Germany.
⁹ Institute of Medical Informatics and Statistics, Kiel University and University Hospital Schleswig-Holstein, Kiel, Germany.
¹⁰ Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
¹¹ Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
¹² DataTecnica LLC, Washington, District of Columbia, USA.
¹³ Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
¹⁴ The Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA.
¹⁵ Neuroscience Research Australia (NeuRA), Randwick, New South Wales, Australia.
¹⁶ Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia.

PMID: 40631485
PMCID: PMC12485575
DOI: 10.1002/mds.30285

No abstract available

Keywords: LRRK2; Parkinson's disease; mitochondria; mitochondrial polygenic score; polygenic score.

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Figures

**FIG. 1**
Associations between mitochondrial polygenic scores (MGS) and Parkinson's disease (PD) status and age‐at‐onset (AAO). (A–C) Violin plots showing the distribution of standardized MGS for patients with idiopathic PD (iPD) and healthy individuals in the European (A) and Ashkenazi Jewish (B) ancestry groups, as well as for patients with *LRRK2*‐PD (C). Boxplots within the violins indicate the median (solid line) and interquartile range (box edges), while the violin shape reflects the overall data distribution. p = t‐test P‐value. (D–F): Receiver operating curves and respective area under the curve values for European (D) and Ashkenazi Jewish (E) ancestry groups, as well as patients with *LRRK2*‐PD (F). (G–I): Correlation plots displaying the association between MGS and AAO in patients with iPD in the European (G) and Ashkenazi Jewish (H) ancestry groups, as well as patients with *LRRK2*‐PD (I). r = Spearman's rank correlation coefficient, p = Spearman's exploratory P‐value. [Color figure can be viewed at wileyonlinelibrary.com]

See this image and copyright information in PMC

Update of

Validation of a Mitochondrial Polygenic Score for Parkinson's Disease.
Ern Ooi JC, Tay YW, Tan AH, Lin CH, Brolin KA, Laabs BH, Sendel S, König IR, Caliebe A, Gabbert C, Andersh KM, Jones L, Lange LM, Fiske B, Sue C, Klein C, Trinh J, Lüth T. Ern Ooi JC, et al. medRxiv [Preprint]. 2025 Mar 19:2025.03.18.25323898. doi: 10.1101/2025.03.18.25323898. medRxiv. 2025. Update in: Mov Disord. 2025 Sep;40(9):2015-2018. doi: 10.1002/mds.30285. PMID: 41030936 Free PMC article. Updated. Preprint.

References

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1. Lüth T, Gabbert C, Koch S, König IR, Caliebe A, Laabs BH, et al. Interaction of mitochondrial polygenic score and lifestyle factors in LRRK2 p.Gly2019Ser Parkinsonism. Mov Disord 2023;38(10):1837–1849. 10.1002/mds.29563 - DOI - PubMed
1. Global Parkinson's Genetics Program , Nalls MA, Blauwendraat C, Bras J, Guerreiro R, Vallerga CL, et al. GP2: the global Parkinson's genetics program. Mov Disord 2021;36(4):842–851. 10.1002/mds.28494 - DOI - PMC - PubMed
1. Rizig M, Bandres‐Ciga S, Makarious MB, Ojo OO, Crea PW, Abiodun OV, et al. Identification of genetic risk loci and causal insights associated with Parkinson's disease in African and African admixed populations: a genome‐wide association study. Lancet Neurol 2023;22(11):1015–1025. 10.1016/S1474-4422(23)00283-1 - DOI - PMC - PubMed

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Evaluation of a Mitochondrial Polygenic Score for Parkinson's Disease Across Ancestries

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Evaluation of a Mitochondrial Polygenic Score for Parkinson's Disease Across Ancestries

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