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Association of GBA Mutations and the E326K Polymorphism With Motor and Cognitive Progression in Parkinson Disease
Davis MY, Johnson CO, Leverenz JB, Weintraub D, Trojanowski JQ, Chen-Plotkin A, Van Deerlin VM, Quinn JF et al.. JAMA neurology, 2016-10-01
Topic: Brain proteins, microglia and lab models
Results Of the total sample of 733 patients who underwent successful genotyping, 226 (30.8%) were women and 507 (69.2%) were men (mean [SD] age, 68.1 [8.8] years). GBA mutations (β = 4.65; 95% CI, 1.72-7.58; P = .002), E326K (β = 3.42; 95% CI, 0.66-6.17; P = .02), and GBA variants combined as a single group (β = 4.01; 95% CI, 1.95-6.07; P = 1.5 × 10-4) were associated with a more rapid decline in MDS-UPDRS III score. Combined GBA variants (β = 0.38; 95% CI, 0.23-0.53; P = .01) and E326K (β = 0.64; 95% CI, 0.43-0.86; P = .002) were associated with faster progression in PIGD scores, but not in tremor scores. A significantly higher proportion of E326K carriers (10 of 21 [47.6%]; P = .01) and GBA variant carriers (15 of 39 [38.5%]; P = .04) progressed to mild cognitive impairment or dementia.
Key findings
- Results Of the total sample of 733 patients who underwent successful genotyping, 226 (30.8%) were women and 507 (69.2%) were men (mean [SD] age, 68.1 [8.8] years).
- GBA mutations (β = 4.65; 95% CI, 1.72-7.58; P = .002), E326K (β = 3.42; 95% CI, 0.66-6.17; P = .02), and GBA variants combined as a single group (β = 4.01; 95% CI, 1.95-6.07; P = 1.5 × 10-4) were associated with a more rapid decline in MDS-UPDRS III score.
- Combined GBA variants (β = 0.38; 95% CI, 0.23-0.53; P = .01) and E326K (β = 0.64; 95% CI, 0.43-0.86; P = .002) were associated with faster progression in PIGD scores, but not in tremor scores.
- A significantly higher proportion of E326K carriers (10 of 21 [47.6%]; P = .01) and GBA variant carriers (15 of 39 [38.5%]; P = .04) progressed to mild cognitive impairment or dementia.
Why it matters
In 733 patients with Parkinson disease, GBA mutations and the E326K polymorphism were associated with more rapid motor decline, and a higher proportion of E326K carriers and GBA variant carriers progressed to mild cognitive impairment or dementia. These findings link genetic variants to faster progression, not to a treatment or cure.
Study details
- Study designlongitudinal study
- Participants740
- Effect size30.8%; 69.2%; 47.6%
- Evidence strengthModerate
How this study scored 66/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (JAMA neurology) |
| Journal's citation record | 2 / 4 | JAMA Neurology: journal h-index 235 (OpenAlex, 2026-10-29) |
| 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 | 1 / 5 | 2016 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 740 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 | 5 / 7 | Cited 218 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 18.2 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 4 / 6 | Cited 14.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 2 / 4 | Cited 46 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Cyrus P. Zabetian: h-index 72 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 15 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 27571329) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 66 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1001/jamaneurol.2016.2245
- PubMed: 27571329
- Original source →
- Free full text: JAMA Neurology →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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.
APA 7th
Davis, M. Y., Johnson, C. O., Leverenz, J. B., Weintraub, D., Trojanowski, J. Q., Chen-Plotkin, A., et al. (2016). Association of GBA Mutations and the E326K Polymorphism With Motor and Cognitive Progression in Parkinson Disease. JAMA neurology. https://doi.org/10.1001/jamaneurol.2016.2245
Vancouver
Davis MY, Johnson CO, Leverenz JB, Weintraub D, Trojanowski JQ, Chen-Plotkin A, et al. Association of GBA Mutations and the E326K Polymorphism With Motor and Cognitive Progression in Parkinson Disease. JAMA neurology. 2016. doi:10.1001/jamaneurol.2016.2245. PMID: 27571329.
BibTeX
@article{davis2016-27571329,
author = {Davis, M. Y. and Johnson, C. O. and Leverenz, J. B. and Weintraub, D. and Trojanowski, J. Q. and Chen-Plotkin, A. and Van Deerlin, V. M. and Quinn, J. F. and others},
title = {{Association of GBA Mutations and the E326K Polymorphism With Motor and Cognitive Progression in Parkinson Disease}},
journal = {JAMA neurology},
year = {2016},
doi = {10.1001/jamaneurol.2016.2245},
pmid = {27571329},
url = {https://doi.org/10.1001/jamaneurol.2016.2245}
}
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