Are rare heterozygous SYNJ1 variants associated with Parkinson's disease?

Konstantin Senkevich^{1

2

3}, Sitki Cem Parlar^{4

5}, Cloe Chantereault^{4

5}, Eric Yu^{4

5}, Jamil Ahmad^{4

6}, Jennifer A Ruskey^{4

6}, Farnaz Asayesh^{4

5}, Dan Spiegelman⁴, Cheryl Waters⁷, Oury Monchi^{6

8

9}, Yves Dauvilliers¹⁰, Nicolas Dupré^{11

12}, Irina Miliukhina¹³, Alla Timofeeva¹⁴, Anton Emelyanov¹⁴, Sofya Pchelina¹⁴, Lior Greenbaum^{15

16

17}, Sharon Hassin-Baer^{15

17

18}, Roy N Alcalay^{7

15

19}, Ziv Gan-Or^{20

21

22}

Affiliations

¹ The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montreal, Quebec, Canada. konstantin.senkevich@mcgill.ca.
² Department of Neurology and neurosurgery, McGill University, Montréal, QC, Canada. konstantin.senkevich@mcgill.ca.
³ Department of Human Genetics, McGill University, Montréal, QC, Canada. konstantin.senkevich@mcgill.ca.
⁴ The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montreal, Quebec, Canada.
⁵ Department of Human Genetics, McGill University, Montréal, QC, Canada.
⁶ Department of Neurology and neurosurgery, McGill University, Montréal, QC, Canada.
⁷ Department of Neurology, College of Physicians and Surgeons, New York, Columbia City, NY, USA.
⁸ Département de radiologie, radio-oncologie et médecine nucléaire, Université de Montréal, Montréal, QC, Canada.
⁹ Centre de recherche de l'Institut universitaire de gériatrie de Montréal, Montréal, QC, Canada.
¹⁰ National Reference Center for Narcolepsy, Sleep Unit, Department of Neurology, Gui-de-Chauliac Hospital, CHU Montpellier, University of Montpellier, Montpellier, France.
¹¹ Neuroscience axis, CHU de Québec-Université Laval, Québec, QC, Canada.
¹² Department of Medicine, Faculty of Medicine, Université Laval, Quebec City, QC, Canada.
¹³ Institute of the Human Brain of RAS, St. Petersburg, Russia.
¹⁴ First Pavlov State Medical University of St. Petersburg, Saint-Petersburg, Russia.
¹⁵ Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
¹⁶ The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel.
¹⁷ The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Israel.
¹⁸ The Movement Disorders Institute, Department of Neurology, Sheba Medical Center, Tel Hashomer, Israel.
¹⁹ Division of Movement Disorders, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
²⁰ The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montreal, Quebec, Canada. ziv.gan-or@mcgill.ca.
²¹ Department of Neurology and neurosurgery, McGill University, Montréal, QC, Canada. ziv.gan-or@mcgill.ca.
²² Department of Human Genetics, McGill University, Montréal, QC, Canada. ziv.gan-or@mcgill.ca.

PMID: 39455605
PMCID: PMC11512049
DOI: 10.1038/s41531-024-00809-9

Are rare heterozygous SYNJ1 variants associated with Parkinson's disease?

Konstantin Senkevich et al. NPJ Parkinsons Dis. 2024.

. 2024 Oct 25;10(1):201.

doi: 10.1038/s41531-024-00809-9.

Authors

Affiliations

¹ The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montreal, Quebec, Canada. konstantin.senkevich@mcgill.ca.
² Department of Neurology and neurosurgery, McGill University, Montréal, QC, Canada. konstantin.senkevich@mcgill.ca.
³ Department of Human Genetics, McGill University, Montréal, QC, Canada. konstantin.senkevich@mcgill.ca.
⁴ The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montreal, Quebec, Canada.
⁵ Department of Human Genetics, McGill University, Montréal, QC, Canada.
⁶ Department of Neurology and neurosurgery, McGill University, Montréal, QC, Canada.
⁷ Department of Neurology, College of Physicians and Surgeons, New York, Columbia City, NY, USA.
⁸ Département de radiologie, radio-oncologie et médecine nucléaire, Université de Montréal, Montréal, QC, Canada.
⁹ Centre de recherche de l'Institut universitaire de gériatrie de Montréal, Montréal, QC, Canada.
¹⁰ National Reference Center for Narcolepsy, Sleep Unit, Department of Neurology, Gui-de-Chauliac Hospital, CHU Montpellier, University of Montpellier, Montpellier, France.
¹¹ Neuroscience axis, CHU de Québec-Université Laval, Québec, QC, Canada.
¹² Department of Medicine, Faculty of Medicine, Université Laval, Quebec City, QC, Canada.
¹³ Institute of the Human Brain of RAS, St. Petersburg, Russia.
¹⁴ First Pavlov State Medical University of St. Petersburg, Saint-Petersburg, Russia.
¹⁵ Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
¹⁶ The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel.
¹⁷ The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Israel.
¹⁸ The Movement Disorders Institute, Department of Neurology, Sheba Medical Center, Tel Hashomer, Israel.
¹⁹ Division of Movement Disorders, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
²⁰ The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montreal, Quebec, Canada. ziv.gan-or@mcgill.ca.
²¹ Department of Neurology and neurosurgery, McGill University, Montréal, QC, Canada. ziv.gan-or@mcgill.ca.
²² Department of Human Genetics, McGill University, Montréal, QC, Canada. ziv.gan-or@mcgill.ca.

PMID: 39455605
PMCID: PMC11512049
DOI: 10.1038/s41531-024-00809-9

Abstract

Previous studies have established that rare biallelic SYNJ1 mutations cause autosomal recessive parkinsonism and Parkinson's disease (PD). We analyzed 8165 PD cases, 818 early-onset-PD (EOPD, < 50 years) and 70,363 controls. Burden meta-analysis revealed an association between rare nonsynonymous variants and variants with high Combined Annotation-Dependent Depletion score (> 20) in the Sac1 SYNJ1 domain and PD (Pfdr = 0.040). A meta-analysis of EOPD patients demonstrated an association between all rare heterozygous SYNJ1 variants and PD (Pfdr = 0.029).

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Conflict of interest statement

Z.G.O. received consultancy fees from Lysosomal Therapeutics Inc. (LTI), Idorsia, Prevail Therapeutics, Ono Therapeutics, Denali, Handl Therapeutics, Neuron23, Bial Biotech, Bial, UCB, Capsida, Vanqua bio, Congruence Therapeutics, Takeda, Jazz Pharmaceuticals, Guidepoint, Lighthouse and Deerfield.

Update of

Are rare heterozygous SYNJ1 variants associated with Parkinson's disease?
Senkevich K, Parlar SC, Chantereault C, Yu E, Ahmad J, Ruskey JA, Asayesh F, Spiegelman D, Waters C, Monchi O, Dauvilliers Y, Dupré N, Miliukhina I, Timofeeva A, Emelyanov A, Pchelina S, Greenbaum L, Hassin-Baer S, Alcalay RN, Gan-Or Z. Senkevich K, et al. medRxiv [Preprint]. 2024 Jun 1:2024.05.29.24307986. doi: 10.1101/2024.05.29.24307986. medRxiv. 2024. Update in: NPJ Parkinsons Dis. 2024 Oct 25;10(1):201. doi: 10.1038/s41531-024-00809-9. PMID: 38853950 Free PMC article. Updated. Preprint.

References

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Are rare heterozygous SYNJ1 variants associated with Parkinson's disease?

Affiliations

Are rare heterozygous SYNJ1 variants associated with Parkinson's disease?

Authors

Affiliations

Abstract

Conflict of interest statement

Update of

References

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