Dataset

This dataset was created by Julian Macnamara

Contents

In May 2023, GP2 announced the fifth data release on the Terra platform in collaboration with AMP® PD.

This release includes 7,462 additional new complex disease participants and 487 new monogenic disease participants, adding to the previous releases from the Complex and Monogenic Networks.

• The complex disease data (genotypes) now consists of a total of 24,935 genotyped participants (12,728 PD cases, 10,533 Controls, and 1,674 ‘Other’ phenotypes).
• The monogenic disease data (whole genome sequences) now consists of a total of 722 sequenced participants.

Please see the accompanying blog for further description of this release. To obtain data access, please see https://amp-pd.org/researchers/data-use-agreement. For any publications using data from this release, please reference the DOI number and the following statement: "Data (DOI 10.5281/zenodo.7904832, release 5) used in the preparation of this article were obtained from the Global Parkinson’s Genetics Program (GP2)."

In July 2025, GP2 announced the 10th data release on the Terra and the Verily® Workbench platforms in collaboration with AMP® PD. This release includes 11,109 additional genotyped participants and 13,339 additional WGS participants.

• The genotype array (NBA) data, including locally-restricted samples, now consists of a total of 82,944 genotyped participants (36,939 PD cases, 19,821 Controls, and 26,184 ‘Other’ phenotypes).
  • When removing the locally-restricted samples, these now consist of 65,303 samples (28,586 PD cases, 15,258 Controls, and 21,459 ‘Other’ phenotypes).
• The whole genome sequencing (WGS) data now consists of a total of 21,073 sequenced participants (8,134 PD cases, 3,531 Controls, and 9,408 ‘Other’ phenotypes).
  • When removing the locally-restricted samples, these now consist of 16,608 participants (6,801 PD cases, 3,244 Controls, and 6,563 ‘Other’ phenotypes).
  • Of note, cases recruited via the Monogenic network are coded as ‘Other’.
• The clinical exome data now consists of 10,454 samples with PD (Release 8).
• Of the 92,021 unique samples with genetic data (NBA, WGS, or clinical exome), 26,982 individuals also have additional extended clinical information.

Please see the accompanying blog for further description of this release. To obtain data access, please see https://amp-pd.org/researchers/data-use-agreement. For any publications using data from this release, please reference the DOI number and the following statement: "Data (DOI 10.5281/zenodo.15748014, release 10) and/or code used in the preparation of this article were obtained from Global Parkinson’s Genetics Program (GP2). GP2 is funded by the Aligning Science Across Parkinson’s (ASAP) initiative and implemented by The Michael J. Fox Foundation for Parkinson’s Research (https://gp2.org). For a complete list of GP2 members see https://gp2.org."

In December 2024, GP2 announced the 9th data release on the Terra and the Verily® Workbench platforms in collaboration with AMP® PD. This release includes 17,690 additional genotyped participants.

• The genotype array data, including locally-restricted samples, now consists of a total of 71,835 genotyped participants (31,985 PD cases, 18,249 Controls, and 21,601 ‘Other’ phenotypes)
  • When removing the locally-restricted samples, these now consist of 55,305 samples (23,709 PD cases, 13,404 Controls, and 18,192 ‘Other’ phenotypes)
• Of those 71,835 samples with genotyped data:
  • 16,800 individuals also have deep clinical phenotyping information (Release 8)
  • 10,454 total individuals also have clinical exomes information (Release 8)
  • 7,732 total individuals also have WGS data (Release 8)

Please see the accompanying blog for further description of this release. To obtain data access, please see https://amp-pd.org/researchers/data-use-agreement. For any publications using data from this release, please reference the DOI number and the following statement: "Data (DOI 10.5281/zenodo.14510099, release 9) and/or code used in the preparation of this article were obtained from Global Parkinson’s Genetics Program (GP2). GP2 is funded by the Aligning Science Across Parkinson’s (ASAP) initiative and implemented by The Michael J. Fox Foundation for Parkinson’s Research (https://gp2.org). For a complete list of GP2 members see https://gp2.org."

Background & AimsThe brain dopaminergic (DA) system is involved in fine tuning many behaviors and several human diseases are associated with pathological alterations of the DA system such as Parkinson’s disease (PD) and drug addiction. Because of its complex network integration, detailed analyses of physiological and pathophysiological conditions are only possible in a whole organism with a sophisticated tool box for visualization and functional modification.Methods & ResultsHere, we have generated transgenic mice expressing the tetracycline-regulated transactivator (tTA) or the reverse tetracycline-regulated transactivator (rtTA) under control of the tyrosine hydroxylase (TH) promoter, TH-tTA (tet-OFF) and TH-rtTA (tet-ON) mice, to visualize and genetically modify DA neurons. We show their tight regulation and efficient use to overexpress proteins under the control of tet-responsive elements or to delete genes of interest with tet-responsive Cre. In combination with mice encoding tet-responsive luciferase, we visualized the DA system in living mice progressively over time.ConclusionThese experiments establish TH-tTA and TH-rtTA mice as a powerful tool to generate and monitor mouse models for DA system diseases.

Background: - T-cells are white blood cells that can find and kill germs and tumors. Cancer can keep T-cells from working. Researchers think a new drug called AMP-224 might help the T-cells in people with cancer. They think the drug might work even better when combined with a certain type of radiation therapy. Objective: - To study the safety and effectiveness of AMP-224 together with 1 or 3 days of stereotactic body radiation therapy (SBRT) directed to the liver. Eligibility: - People age 18 and older with metastatic colorectal cancer. Their cancer must have spread to the liver and not be responding to treatment. Design: * Participants will be screened with a medical history, physical exam, and blood and urine tests. Their tumors will be measured with computerized tomography (CT) scans or magnetic resonance imaging (MRI) of the chest, stomach, and pelvis. They will have an electrocardiogram (ECG) heart test. * Participants will have a small part of their tumor removed by needle (biopsy). * Participants will have 8 study visits over about 10 weeks. * At 1 visit, they will have another tumor biopsy. * At 1 visit, they will get a chemotherapy drug through a vein (intravenous (IV)). * At 6 visits, they will receive AMP-224 through an IV. * At 1 or 3 visits, they will have SBRT. Computed tomography (CT) scans will map the position of their tumor. Radiation beams of different intensities at different angles will be directed to the tumor. * At all visits, some screening procedures may be repeated. * After treatment ends, participants will have 7 follow-up visits over about 5 months. Blood will be drawn. Some screening procedures may be repeated.

The aggregation and transmission of SNCA/α-synuclein (synuclein, alpha) is a hallmark pathology of Parkinson disease (PD). PLK2 (polo like kinase 2) is an evolutionarily conserved serine/threonine kinase that is more abundant in the brains of all family members, is highly expressed in PD, and is linked to SNCA deposition. However, in addition to its role in phosphorylating SNCA, the role of PLK2 in PD and the mechanisms involved in triggering neurodegeneration remain unclear. Here, we found that PLK2 regulated SNCA pathology independently of S129. Overexpression of PLK2 promoted SNCA preformed fibril (PFF)-induced aggregation of wild-type SNCA and mutant SNCAS129A. Genetic or pharmacological inhibition of PLK2 attenuated SNCA deposition and neurotoxicity. Mechanistically, PLK2 exacerbated the propagation of SNCA pathology by impeding the clearance of SNCA aggregates by blocking macroautophagic/autophagic flux. We further showed that PLK2 phosphorylated S1098 of DCTN1 (dynactin 1), a protein that controls the movement of organelles, leading to impaired autophagosome-lysosome fusion. Furthermore, genetic suppression of PLK2 alleviated SNCA aggregation and motor dysfunction in vivo. Our findings suggest that PLK2 negatively regulates autophagy, promoting SNCA pathology, suggesting a role for PLK2 in PD. Abbreviation: AD: Alzheimer disease; AMPK: AMP-activated protein kinase; CASP3: caspase 3; DCTN1: dynactin 1; LBs: lewy bodies; LDH: lactate dehydrogenase; LAMP1: lysosomal associated membrane protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAP2: microtubule associated protein 2; MTOR: mechanistic target of rapamycin kinase; NH4Cl: ammonium chloride; p-SNCA: phosphorylation of SNCA at S129; PD: Parkinson disease; PFF: preformed fibril; PI: propidium iodide; PLK2: polo like kinase 2; PRKAA/AMPK: protein kinase AMP-activated catalytic subunit alpha; shRNA: short hairpin RNA; SNCA: synuclein, alpha; SQSTM1/p62: sequestosome 1; TH: tyrosine hydroxylase; TX: Triton X-100; ULK1: unc-51 like autophagy activating kinase 1.