Polygenic scores for longevity in relation to brain MRI measures in a cohort of 70-year-olds
Population-based studies on the relation between polygenic longevity scores (PGLSs) and specific brain regions on magnetic resonance imaging (MRI) are few. We aimed to investigate this relationship in a population of 70-year-olds from Gothenburg, Sweden (N = 675). We constructed two PGLSs (one with and one without the APOE locus) using longevity GWAS summary statistics. MRI outcomes included total grey matter, white matter (WM), WM hyperintensities (WMHs), subcortical volumes, small vessel disease (SVD) score, cortical thicknesses, and fractional anisotropy (FA) fibre tracts. We adjusted for sex, age, principal components, and sex interactions, and corrected for multiple comparisons. We found no associations in the total sample. In males, both PGLSs were associated with smaller WMHs volume and lower SVD burden, and a thicker cortex of pars triangularis, pars opercularis, and insula. Our findings suggest a possible link between genetic propensity for longevity and lower cerebrovascular burden and certain cortical grey matter areas in males.
Authors
- Nazib M. Seidu (ORCID: https://orcid.org/0000-0002-8381-9657)
- Nira Cedrés (ORCID: https://orcid.org/0000-0002-1850-6451)
- Olof E. Lindberg (ORCID: https://orcid.org/0000-0001-6352-108X)
- Lars‐Olof Wahlund (ORCID: https://orcid.org/0000-0002-9905-8426)
- Margda Wærn (ORCID: https://orcid.org/0000-0002-8330-6915)
- Anna Zettergren (ORCID: https://orcid.org/0000-0002-7182-8417)
- Ingmar Gr. Skoog (ORCID: https://orcid.org/0000-0002-9803-3438)
- Silke Kern (ORCID: https://orcid.org/0000-0001-7617-7214)
- Eric Westman (ORCID: https://orcid.org/0000-0002-3115-2977)
- Lina Rydén (ORCID: https://orcid.org/0000-0002-3817-2620)
- Rosaleena Mohanty (ORCID: https://orcid.org/0000-0001-6499-1251)
- Henrik Zetterberg (ORCID: https://orcid.org/0000-0002-4671-6763)
- Kaj Blennow
- Henne Holstege
- Hanna Falk Erhag
Institutions
- University of Wisconsin–Madison (US)
- Stockholm University (SE)
- University of Calgary (CA)
- Sahlgrenska University Hospital (SE)
- Karolinska Institutet (SE)
- Universidad Fernando Pessoa Canarias (ES)
- Public Dental Service Västra Götaland (SE)
- Region Västra Götaland (SE)
- Amsterdam Neuroscience (NL)
- UK Dementia Research Institute (GB)
- Amsterdam University Medical Centers (NL)
- UCL Queen Square Institute of Neurology (GB)
- Hotchkiss Brain Institute (CA)
- University College London (GB)
- Imperial College London (GB)
- Vrije Universiteit Amsterdam (NL)
- University of Gothenburg (SE)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Delft University of Technology (NL)
Publication Details
- Journal
- npj Aging
- Published
- 2026-10-15
- DOI
- https://doi.org/10.1038/s41514-026-00546-8
- Primary Topic
- Genetic Associations and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Eli Lilly and Company
- Biogen
- Parkinson's Foundation
- Eisai
- Hjärnfonden
- Karolinska Institutet
- Novo Nordisk
- Stockholms Läns Landsting
- Vetenskapsrådet
- Göteborgs Universitet
- Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse
- Stiftelsen Psykiatriska Forskningsfonden
- Alzheimerfonden
- Parkinsonfonden
- Center for Innovative Medicine
- Eivind och Elsa K:son Sylvans stiftelse