Evidence map›Paper›PMID 41857676›Full record

ArticleAlzheimer's research & therapy2026

Interactive effects of telomere length and genetic variants on Alzheimer disease risk across multiple ancestral populations.

Zainab Khurshid, Tong Tong, Oluwatosin Olayinka, John J Farrell, Congcong Zhu, Alzheimer’s Disease Sequencing Project, Eden R Martin, William S Bush, Margaret A Pericak-Vance, Li-San Wang and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's research & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Zainab KhurshidBioinformatics Program, Boston University, Boston, MA, 02215, USA.
Tong TongBioinformatics Program, Boston University, Boston, MA, 02215, USA.
Oluwatosin OlayinkaBioinformatics Program, Boston University, Boston, MA, 02215, USA.
John J FarrellDepartment of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA, 02118, USA.
Congcong ZhuDepartment of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA, 02118, USA.
Alzheimer’s Disease Sequencing Project
Eden R MartinHussman Institute of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
William S BushDepartment of Population and Quantitative Health Sciences Case, Western Reserve University, Cleveland, OH, 44106, USA.
Margaret A Pericak-VanceHussman Institute of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
Li-San WangDepartment of Pathology and Laboratory Medicine, Penn Neurodegeneration Genomics Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Gerard D SchellenbergDepartment of Pathology and Laboratory Medicine, Penn Neurodegeneration Genomics Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Jonathan L HainesDepartment of Population and Quantitative Health Sciences Case, Western Reserve University, Cleveland, OH, 44106, USA.
Kathryn L LunettaDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, 02118, USA.
Xiaoling Zhang *Bioinformatics Program, Boston University, Boston, MA, 02215, USA. zhangxl@bu.edu.
Lindsay A Farrer *Bioinformatics Program, Boston University, Boston, MA, 02215, USA. farrer@bu.edu.

Funding

NIA NIH HHS R01-AG048927NIA NIH HHS U01-AG072577
6 · The paper itself

Abstract

backgroundTelomere length (TL), a biomarker of biological aging, but its association with Alzheimer’s disease (AD) remains unclear.

methodsWe estimated TL in whole-genome sequencing data from 35,014 Alzheimer’s Disease Sequencing Project participants using TelSeq, which after quality control yielded a dataset including 6,973 persons of European ancestry (EA), 4,188 African Americans (AA), 4,005 Caribbean Hispanics (CH), and 4,170 Native American Hispanics (NAH). TL was log-transformed, adjusted for age and blood cell counts, and z-scaled. Scaled TL was dichotomized into long (TL > 0) and short (TL ≤ 0) groups. An AD GWAS for the interaction of TL with variants having a minor allele count > 20 was performed in each ancestry group using logistic regression models including SNP and TL main effects and a SNP × TL interaction term.

resultsAD 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.

conclusionWe identified variants that significantly impact AD risk through their interaction with TL, suggesting that TL maintenance pathways may be central to AD pathogenesis.

Indexed as

Alzheimer DiseaseGenetic Predisposition to DiseaseTelomereAgedBlack or African AmericanCaribbean PeopleFemaleGenetic VariationGenome-Wide Association StudyHispanic or LatinoHumansMalePolymorphism, Single NucleotideWhiteWhole Genome SequencingAlzheimer’s diseaseElomere lengthGenetic variantsWhole genome sequencing

Identifiers

PMID41857676
PMCPMC13122948

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.