Genome-wide survival study identifies a novel synaptic locus and polygenic score for cognitive progression in Parkinson's disease
Liu G, Peng J, Liao Z, Locascio JJ, Corvol JC, Zhu F, Dong X, Maple-Grødem J et al.. Nature genetics, 2021-05-06
Topic: Brain proteins, microglia and lab models
A key driver of patients' well-being and clinical trials for Parkinson's disease (PD) is the course that the disease takes over time (progression and prognosis). To assess how genetic variation influences the progression of PD over time to dementia, a major determinant for quality of life, we performed a longitudinal genome-wide survival study of 11.2 million variants in 3,821 patients with PD over 31,053 visits. We discover RIMS2 as a progression locus and confirm this in a replicate population (hazard ratio (HR) = 4.77, P = 2.78 × 10 -11 ), identify suggestive evidence for TMEM108 (HR = 2.86, P = 2.09 × 10 -8 ) and WWOX (HR = 2.12, P = 2.37 × 10 -8 ) as progression loci, and confirm associations for GBA (HR = 1.93, P = 0.0002) and APOE (HR = 1.48, P = 0.001). Polygenic progression scores exhibit a substantial aggregate association with dementia risk, while polygenic susceptibility scores are not predictive. This study identifies a novel synaptic locus and polygenic score for cognitive disease progression in PD and proposes diverging genetic architectures of progression and susceptibility.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Liu, G., Peng, J., Liao, Z., Locascio, J. J., Corvol, J. C., Zhu, F., et al. (2021). Genome-wide survival study identifies a novel synaptic locus and polygenic score for cognitive progression in Parkinson's disease. Nature genetics. https://doi.org/10.1038/s41588-021-00847-6
Vancouver
Liu G, Peng J, Liao Z, Locascio JJ, Corvol JC, Zhu F, et al. Genome-wide survival study identifies a novel synaptic locus and polygenic score for cognitive progression in Parkinson's disease. Nature genetics. 2021. doi:10.1038/s41588-021-00847-6. PMID: 33958783.
BibTeX
@article{liu2021-33958783,
author = {Liu, G. and Peng, J. and Liao, Z. and Locascio, J. J. and Corvol, J. C. and Zhu, F. and Dong, X. and Maple-Grødem, J. and others},
title = {{Genome-wide survival study identifies a novel synaptic locus and polygenic score for cognitive progression in Parkinson's disease}},
journal = {Nature genetics},
year = {2021},
doi = {10.1038/s41588-021-00847-6},
pmid = {33958783},
url = {https://doi.org/10.1038/s41588-021-00847-6}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- A key driver of patients' well-being and clinical trials for Parkinson's disease (PD) is the course that the disease takes over time (progression and prognosis).
- To assess how genetic variation influences the progression of PD over time to dementia, a major determinant for quality of life, we performed a longitudinal genome-wide survival study of 11.2 million variants in 3,821 patients with PD over 31,053 visits.
- We discover RIMS2 as a progression locus and confirm this in a replicate population (hazard ratio (HR) = 4.77, P = 2.78 × 10 -11 ), identify suggestive evidence for TMEM108 (HR = 2.86, P = 2.09 × 10 -8 ) and WWOX (HR = 2.12, P = 2.37 × 10 -8 ) as progression loci, and confirm associations for GBA (HR = 1.93, P = 0.0002) and APOE (HR = 1.48, P = 0.001).
- Polygenic progression scores exhibit a substantial aggregate association with dementia risk, while polygenic susceptibility scores are not predictive.
- This study identifies a novel synaptic locus and polygenic score for cognitive disease progression in PD and proposes diverging genetic architectures of progression and susceptibility.
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Study details
- Study designlongitudinal study
- Participants3,821
- Effect sizeHR = 2.86; HR = 2.12; HR = 1.93
- Evidence strengthModerate
How this study scored 78/100
Published in a leading specialty journal, and it is a longitudinal study following the same people over time. Scored zero for randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 45 of the 58 points we could judge it on, which is 78 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature genetics) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 3 / 4 | 3,821 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33958783) |
| Free to read | 2 / 2 | Free to read |
| Points | 45 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 45 of the 58 points we could judge it on is 78 out of 100. |
| Total | 78 / 100 | — |
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