Evidence map›Paper›PMID 41998431›Full record

ArticleGeroScience2026

Interactions between rare variants in DNA repair genes and cardiometabolic risk explain more variability in cognitive function.

Nicolas Cherbuin, Leticia Camargo Tavares, Mark A Fraser, Yuan Li, Claudia Navarro, Erin I Walsh, Shea J Andrews, Richard A Burns, Anne Brüstle, Lene Juel Rasmussen

Abstract read
PubMed Publisher
In one paragraph

Article in GeroScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Nicolas CherbuinNational Centre for Epidemiology and Population Health, Australian National University, Canberra, Australia. nicolas.cherbuin@anu.edu.au.ORCID http://orcid.org/0000-0001-6481-0748
Leticia Camargo TavaresNational Centre for Epidemiology and Population Health, Australian National University, Canberra, Australia.ORCID http://orcid.org/0000-0001-7278-0999
Mark A FraserNational Centre for Epidemiology and Population Health, Australian National University, Canberra, Australia.ORCID http://orcid.org/0000-0001-7795-7968
Yuan LiDepartment of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0001-8275-2916
Claudia NavarroDepartment of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-2393-7512
Erin I WalshNational Centre for Epidemiology and Population Health, Australian National University, Canberra, Australia.ORCID http://orcid.org/0000-0001-8941-0046
Shea J AndrewsDepartment of Psychiatry and Behavioral Sciences, University of California, San Francisco, USA.ORCID http://orcid.org/0000-0002-1921-9470
Richard A BurnsNational Centre for Epidemiology and Population Health, Australian National University, Canberra, Australia.ORCID http://orcid.org/0000-0002-7750-4341
Anne BrüstleJohn Curtin School of Medical Research, Australian National University, Canberra, Australia.ORCID http://orcid.org/0000-0002-3842-5683
Lene Juel RasmussenDepartment of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0001-6864-963X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The brain is vulnerable to DNA damage and cardiometabolic risk. Yet, whether genetic variation in DNA repair interacts with cardiometabolic factors to explain cognitive variability remains unclear. Participants (n = 376,533) of white-British ancestry from the UK biobank with cognitive, neuroimaging, and whole-exome sequencing data were included. Six cognitive outcomes were assessed: fluid intelligence (FIQ), symbol-digit matching task (SDMT), visual matching (MATCH), trail making (TRAIL1 and TRAIL2), and prospective memory (PMEM). Seven brain regions of interest were assessed: total brain (TBV), grey matter (GMV), left and right white matter (LWM/RWM), left and right hippocampi (LHC/RHC), and white matter hyperintensities (WMH) volumes. A total of 3487 genetic variants across 39 DNA repair genes were tested. SNP and gene/gene-set level associations were tested using regression models adjusted for age, sex, APOE ε4, ancestry, and outcome-specific covariates. Genetic interactions with a multidimensional cardiometabolic risk index (CMRI), encompassing established risk factors, were assessed. We detected 107 genetic variants (mostly extremely rare) across 36 DNA repair genes associated at Bonferroni-significance (p ≤ 1.4 × 10

Indexed as

Brain ageingCognitive declineDNA repairInflammationOxidative stressSingle-nucleotide polymorphism

Identifiers

PMID41998431

What Socratic holds

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Read underepoch 390

Registered trials

None linked

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.