Genetic modifiers of risk and age at onset in GBA associated Parkinson's disease and Lewy body dementia
Blauwendraat C, Reed X, Krohn L, Heilbron K, Bandres-Ciga S, Tan M, Gibbs JR, Hernandez DG et al.. Brain : a journal of neurology, 2020-01-01
Topic: Genetics and APOE
Variants in GBA, encoding the enzyme glucocerebrosidase, are associated with Lewy body diseases such as Parkinson's disease and Lewy body dementia. We attempted to replicate our findings in two independent datasets, including the personal genetics company 23andMe, Inc. and whole-genome sequencing data. Our analysis showed that the overall Parkinson's disease genetic risk score modifies risk for disease and decreases age at onset in carriers of GBA variants. Dissecting this signal demonstrated that variants in close proximity to SNCA and CTSB (encoding cathepsin B) are the most significant contributors. Additional analyses suggest a possible genetic interaction between GBA and CTSB and GBA p.N370S induced pluripotent cell-derived neurons were shown to have decreased cathepsin B expression compared to controls. Further, these results have implications for selection of GBA carriers for therapeutic interventions.
Key findings
- Variants in GBA, encoding the enzyme glucocerebrosidase, are associated with Lewy body diseases such as Parkinson's disease and Lewy body dementia.
- We attempted to replicate our findings in two independent datasets, including the personal genetics company 23andMe, Inc. and whole-genome sequencing data.
- Our analysis showed that the overall Parkinson's disease genetic risk score modifies risk for disease and decreases age at onset in carriers of GBA variants.
- Dissecting this signal demonstrated that variants in close proximity to SNCA and CTSB (encoding cathepsin B) are the most significant contributors.
- Additional analyses suggest a possible genetic interaction between GBA and CTSB and GBA p.N370S induced pluripotent cell-derived neurons were shown to have decreased cathepsin B expression compared to controls.
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Study details
- Study designcase-control study
- Participants165
- Evidence strengthModerate
How this study scored 64/100
Published in a leading specialty journal, and it is a case-control study. Scored zero for effect reported and 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 37 of the 58 points we could judge it on, which is 64 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain : a journal of neurology) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 6 / 12 | A case-control study |
| 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 | 2 / 5 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 2 / 4 | 165 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| 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 31755958) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 37 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 37 of the 58 points we could judge it on is 64 out of 100. |
| Total | 64 / 100 | — |
What each of these 20 components measures, and what this score is not →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Blauwendraat, C., Reed, X., Krohn, L., Heilbron, K., Bandres-Ciga, S., Tan, M., et al. (2020). Genetic modifiers of risk and age at onset in GBA associated Parkinson's disease and Lewy body dementia. Brain : a journal of neurology. https://doi.org/10.1093/brain/awz350
Vancouver
Blauwendraat C, Reed X, Krohn L, Heilbron K, Bandres-Ciga S, Tan M, et al. Genetic modifiers of risk and age at onset in GBA associated Parkinson's disease and Lewy body dementia. Brain : a journal of neurology. 2020. doi:10.1093/brain/awz350. PMID: 31755958.
BibTeX
@article{blauwendraat2020-31755958,
author = {Blauwendraat, C. and Reed, X. and Krohn, L. and Heilbron, K. and Bandres-Ciga, S. and Tan, M. and Gibbs, JR. and Hernandez, D. G. and others},
title = {{Genetic modifiers of risk and age at onset in GBA associated Parkinson's disease and Lewy body dementia}},
journal = {Brain : a journal of neurology},
year = {2020},
doi = {10.1093/brain/awz350},
pmid = {31755958},
url = {https://doi.org/10.1093/brain/awz350}
}
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