Interactive effects of telomere length and genetic variants on Alzheimer disease risk across multiple ancestral populations
Zainab Khurshid, Tong Tong, Oluwatosin A Olayinka, John Joseph Farrell, Congcong Zhu, Alzheimer's Disease Sequencing Project, Eden R. Martin, William S. Bush et al.. Alzheimer s Research & Therapy, 2026-03-20
Topic: Amyloid, tau and blood-test diagnosis
AD risk was associated with shorter TL (β = -0.48, P < 2 × 10–16). Longer and shorter TL were associated with dosages of APOE ε2 (P = 3.40 × 10–4) and ε4 (P = 7.05 × 10–3), respectively. In the EA group, genome-wide significant (GWS) TL × SNP interactions were identified for variants in SEMA6A (P = 1.42 × 10–8) and LOC105378654 (P = 4.17 × 10–8), between IL15 and INPP4B (P = 1.77 × 10–8) and upstream of RP11-2N5.2 (P = 4.60 × 10–8). In the NAH group, GWS interactions were observed with an intronic variant in BSN (P = 3.26 × 10–8) and missense variant in MST1 (P = 3.26 × 10–8). In the total sample, interactions with variants between CTD-2160D9.1 and EEF1A1P20 (P < 1.19 × 10–8), in TBC1D22A (P = 1.06 × 10–8) and in PLK1 (P = 3.28 × 10–8) were GWS. We identified variants that significantly impact AD risk through their interaction with TL, suggesting that TL maintenance pathways may be central to AD pathogenesis.
Key findings
- AD risk was associated with shorter TL (β = -0.48, P < 2 × 10–16).
- Longer and shorter TL were associated with dosages of APOE ε2 (P = 3.40 × 10–4) and ε4 (P = 7.05 × 10–3), respectively.
- In the EA group, genome-wide significant (GWS) TL × SNP interactions were identified for variants in SEMA6A (P = 1.42 × 10–8) and LOC105378654 (P = 4.17 × 10–8), between IL15 and INPP4B (P = 1.77 × 10–8) and upstream of RP11-2N5.2 (P = 4.60 × 10–8).
- In the NAH group, GWS interactions were observed with an intronic variant in BSN (P = 3.26 × 10–8) and missense variant in MST1 (P = 3.26 × 10–8).
- In the total sample, interactions with variants between CTD-2160D9.1 and EEF1A1P20 (P < 1.19 × 10–8), in TBC1D22A (P = 1.06 × 10–8) and in PLK1 (P = 3.28 × 10–8) were GWS.
Why it matters
Shorter telomere length was associated with Alzheimer's disease risk, and genome-wide significant interactions between telomere length and genetic variants were identified across multiple ancestral populations. These findings suggest that telomere maintenance pathways may be central to Alzheimer's pathogenesis.
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Study details
- Participants6,973
- Evidence strengthLow
How this study scored 42/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer s Research & Therapy) |
| Journal's citation record | 1 / 4 | Alzheimer s Research & Therapy: journal h-index 146 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” 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 | 3 / 4 | 6,973 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 | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 0 / 6 | Cited 0.0× 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 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Lindsay A. Farrer: h-index 119 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Pennsylvania: institution h-index 1,859 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41857676) |
| Free to read | 2 / 2 | Free to read |
| Total | 42 / 100 | — |
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Read the original
- DOI: 10.1186/s13195-026-02005-8
- PubMed: 41857676
- Original source →
- Free full text: Alzheimer s Research & Therapy →
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
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APA 7th
Khurshid, Z., Tong, T., Olayinka, O. A., Farrell, J. J., Zhu, C., Alzheimer's Disease Sequencing Project, et al. (2026). Interactive effects of telomere length and genetic variants on Alzheimer disease risk across multiple ancestral populations. Alzheimer s Research & Therapy. https://doi.org/10.1186/s13195-026-02005-8
Vancouver
Khurshid Z, Tong T, Olayinka OA, Farrell JJ, Zhu C, Alzheimer's Disease Sequencing Project, et al. Interactive effects of telomere length and genetic variants on Alzheimer disease risk across multiple ancestral populations. Alzheimer s Research & Therapy. 2026. doi:10.1186/s13195-026-02005-8. PMID: 41857676.
BibTeX
@article{khurshid2026-41857676,
author = {Khurshid, Zainab and Tong, Tong and Olayinka, Oluwatosin A and Farrell, John Joseph and Zhu, Congcong and {Alzheimer's Disease Sequencing Project} and Martin, Eden R. and Bush, William S. and others},
title = {{Interactive effects of telomere length and genetic variants on Alzheimer disease risk across multiple ancestral populations}},
journal = {Alzheimer s Research \& Therapy},
year = {2026},
doi = {10.1186/s13195-026-02005-8},
pmid = {41857676},
url = {https://doi.org/10.1186/s13195-026-02005-8}
}
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