Population Attributable Risk in Alzheimer and Parkinson Diseases
Lietsel Jones, Catalina Cerquera‐Cleves, Artur Francisco Schumacher Schuh, Mary B. Makarious, Hirotaka Iwaki, Mike A. Nalls, Alastair John Noyce, Cornelis Blauwendraat et al.. Neurology Genetics, 2026-07-16
Topic: Amyloid, tau and blood-test diagnosis
ObjectivesEmerging evidence suggests that the genetic architecture of Alzheimer disease (AD) and Parkinson disease (PD) risk varies across ancestries. This study seeks to explore distinct and universal genetic targets across individuals of Latino, African/African-admixed, East Asian, and European populations by implementing population attributable risk (PAR) comparisons using summary statistics from genome-wide association studies (GWASs). MethodsPAR was calculated for the most significant disease variants using summary statistics derived from select multi-ancestry GWAS meta-analyses, followed by fine-mapping analysis to validate genetic contribution of disease variants to European, African/African-admixed, East Asian, and Latino individuals. ResultsFor AD, APOE4 PAR estimates were universally high across all ancestries, with TSPAN14 and PICALM emerging as other common targets. Attributable risk varied across PD-related major risk loci, including variation nearby GBA1 and LRRK2. By contrast, SNCA, MCCC1, VPS13C, and MAPT loci demonstrated comparable attributable risk across ancestries. DiscussionThis cross-ancestry evaluation of PAR reinforces the genetic heterogeneity of AD and PD. In consideration of the complex etiology of these diseases, these findings may inform the strategic prioritization of therapeutic targets and improve global health outcomes.
Key findings
- ObjectivesEmerging evidence suggests that the genetic architecture of Alzheimer disease (AD) and Parkinson disease (PD) risk varies across ancestries.
- MethodsPAR was calculated for the most significant disease variants using summary statistics derived from select multi-ancestry GWAS meta-analyses, followed by fine-mapping analysis to validate genetic contribution of disease variants to European, African/African-admixed, East Asian, and Latino individuals.
- By contrast, SNCA, MCCC1, VPS13C, and MAPT loci demonstrated comparable attributable risk across ancestries.
- In consideration of the complex etiology of these diseases, these findings may inform the strategic prioritization of therapeutic targets and improve global health outcomes.
Why it matters
This analysis found that APOE4 attributable risk for Alzheimer disease was universally high across ancestries, with TSPAN14 and PICALM as other common targets. The authors say these findings may help prioritize therapeutic targets, but no treatment was tested.
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Study details
- Study designmeta-analysis
- Evidence strengthHigh
How this study scored 55/100
Published in a peer-reviewed journal, and it is a meta-analysis pooling many studies. Scored zero for sample size, effect reported and studied in people because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 53 of the 96 points we could judge it on, which is 55 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurology Genetics) |
| Journal's citation record | 0 / 4 | Neurology Genetics: journal h-index 53 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | A review of other studies — randomisation is not credited here |
| Times cited | 1 / 7 | Cited 1 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 3 / 6 | Cited 4.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | OpenAlex's profile for last-listed author as the Global Parkinson's Genetics Program (GP2) holds only 2 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 3 / 3 | National Institutes of Health: institution h-index 2,723 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 12 institution(s) in 5 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42639394) |
| Free to read | 2 / 2 | Free to read |
| Points | 53 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 53 of the 96 points we could judge it on is 55 out of 100. |
| Total | 55 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1212/nxg.0000000000200415
- PubMed: 42639394
- Original source →
- Free full text: Neurology Genetics →
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
Jones, L., Cerquera‐Cleves, C., Schuh, A. F. S., Makarious, M. B., Iwaki, H., Nalls, M. A., et al. (2026). Population Attributable Risk in Alzheimer and Parkinson Diseases. Neurology Genetics. https://doi.org/10.1212/nxg.0000000000200415
Vancouver
Jones L, Cerquera‐Cleves C, Schuh AFS, Makarious MB, Iwaki H, Nalls MA, et al. Population Attributable Risk in Alzheimer and Parkinson Diseases. Neurology Genetics. 2026. doi:10.1212/nxg.0000000000200415. PMID: 42639394.
BibTeX
@article{jones2026-42639394,
author = {Jones, Lietsel and Cerquera‐Cleves, Catalina and Schuh, Artur Francisco Schumacher and Makarious, Mary B. and Iwaki, Hirotaka and Nalls, Mike A. and Noyce, Alastair John and Blauwendraat, Cornelis and others},
title = {{Population Attributable Risk in Alzheimer and Parkinson Diseases}},
journal = {Neurology Genetics},
year = {2026},
doi = {10.1212/nxg.0000000000200415},
pmid = {42639394},
url = {https://doi.org/10.1212/nxg.0000000000200415}
}
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