The genetic architecture of Parkinson’s disease on the Island of Crete
We investigated the genetic landscape of Parkinson's disease (PD) on the island of Crete. DNA samples from 360 PD patients and 251 controls were analyzed using a combination of genotyping, whole-exome sequencing, and targeted screening for GBA1 variants p.N409S and p.L483P. A molecular diagnosis (heterozygous dominant/homozygous recessive pathogenic/likely pathogenic non-GBA1 variant) was identified in 3.1% of patients, including LRRK2-PD (n = 4) and SNCA-PD (n = 1). A novel homozygous PINK1 variant (p.Y295Ter) and a rare homozygous FIG4 variant (p.I41T) were detected in two early-onset cases. About 10.3% of patients carried a GBA1 variant, including four rare variants (p.C55S, p.H294Q, p.K237T, p.R502H), and had an adjusted earlier disease onset of 7.3 years. GBA1 carriers had a 4.3-fold higher risk for PD compared to non-carriers. The proportion of GBA1 in Crete is substantially higher than on the Greek mainland, highlighting the distinct genetic PD profile in this population and supporting targeted genetic testing and counseling.
Authors
- Nikolaos M. Marinakis (ORCID: https://orcid.org/0000-0002-7078-3253)
- Anindita Ray (ORCID: https://orcid.org/0000-0003-4824-8913)
- Georgia Xiromerisiou (ORCID: https://orcid.org/0000-0001-7162-3588)
- Cleanthe Spanaki (ORCID: https://orcid.org/0000-0001-9824-6620)
- Ruth Chia (ORCID: https://orcid.org/0000-0002-4709-7423)
- Panayiotis Mitsias (ORCID: https://orcid.org/0000-0002-9089-4954)
- Shaimaa Sait
- Sonja W. Scholz (ORCID: https://orcid.org/0000-0002-6623-0429)
- Giannis Vatsellas (ORCID: https://orcid.org/0000-0002-1631-1060)
- Iro Boura (ORCID: https://orcid.org/0000-0002-9110-6833)
- Periklis Makrythanasis (ORCID: https://orcid.org/0000-0002-3725-0113)
- Arvind Kumar (ORCID: https://orcid.org/0000-0002-9608-8267)
- Theodoros Loupis
- Vasiliki Pavlaki
Institutions
- University of Geneva (CH)
- University of Crete (GR)
- Johns Hopkins University (US)
- Democritus University of Thrace (GR)
- Wayne State University (US)
- National and Kapodistrian University of Athens (GR)
- Academy of Athens (GR)
- Johns Hopkins Medicine (US)
- Henry Ford Hospital (US)
- Biomedical Research Foundation of the Academy of Athens (GR)
- MIND Research Institute (US)
- National Institute of Neurological Disorders and Stroke (US)
- National Institute on Aging (US)
- University Hospital of Heraklion (GR)
- Institute of Aging (CA)
Publication Details
- Journal
- npj Parkinson s Disease
- Published
- 2025-12-18
- DOI
- https://doi.org/10.1038/s41531-025-01192-9
- Primary Topic
- Lysosomal Storage Disorders Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- U.S. Department of Health and Human Services
- European Commission
- University of Crete
- National Institutes of Health
- HORIZON EUROPE Framework Programme