Evidence map›Paper›PMID 41066301›Full record

ArticleThe journals of gerontology. Series A, Biological sciences and medical sciences2025

A genome-wide association study identified 10 novel genomic loci associated with intrinsic capacity.

Melkamu B Beyene, Renuka Visvanathan, Robel Alemu, Beben Benyamin, Rudrarup Bhattacharjee, Habtamu B Beyene, Olga Theou, Matteo Cesari, John R Beard, Azmeraw T Amare

Erratum issuedAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in The journals of gerontology. Series A, Biological sciences and medical sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Associations and interaction effects of socioeconomic, lifestyle, and genetic factors on intrinsic capacity.The journals of gerontology. Series A, Biological sciences and medical sciences · 2026
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Melkamu B BeyeneDiscipline of Psychiatry, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia.ORCID 0000-0003-4349-9887
Renuka VisvanathanAdelaide Geriatrics Training and Research with Aged Care Centre (GTRAC), University of Adelaide, and the Basil Hetzel Institute, Adelaide, SA, Australia.ORCID 0000-0002-1303-9479
Robel AlemuDiscipline of Psychiatry, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia.
Beben BenyaminAustralian Centre for Precision Health, Allied Health and Human Performance, University of South Australia, Adelaide, Australia.
Rudrarup BhattacharjeeAdelaide Centre for Epigenetics, School of Biomedicine, The University of Adelaide, Adelaide, SA, Australia.
Habtamu B BeyeneMetabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia.
Olga TheouPhysiotherapy and Geriatric Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.ORCID 0000-0001-6460-782X
Matteo CesariAgeing and Health Unit, Department of Maternal, Newborn, Child & Adolescent Health and Ageing, World Health Organization, Geneva, Switzerland.ORCID 0000-0002-0348-3664
John R BeardInternational Longevity Centre USA, Columbia University Mailman School of Public Health, New York, United States.
Azmeraw T AmareDiscipline of Psychiatry, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia.ORCID 0000-0002-7940-0335

Funding

Emerging Leadership APP2008000National Health and Medical Research CouncilUniversity of AdelaideWorld Health Organization 001
6 · The paper itself

Abstract

backgroundIntrinsic capacity (IC) is a multidimensional concept within the World Health Organization framework for healthy aging. It refers to the composite of an individual's physical and mental capacities that enable them to maintain well-being, functional ability, and engagement in valued activities throughout life. While substantial evidence supports the biological basis of IC and its subdomains, the extent to which genetic factors influence IC remains largely unexplored, with no studies currently available.

methodsUsing datasets from the UK Biobank (UKB; N = 44 631) and the Canadian Longitudinal Study on Aging (CLSA; N = 13 085), we implemented the restricted maximum likelihood method to estimate SNP-based heritability (h2snp), followed by a Genome-Wide Association Study (GWAS) to identify genetic variants associated with IC, and post-GWAS analyses to pinpoint biological implications.

resultsThe h2snp for IC was estimated at 25.2% in UKB and 19.5% in CLSA. Our GWAS identified 38 independent SNPs for IC across 10 genomic loci and 4289 candidate SNPs, mapped to 197 genes. Post-GWAS analysis revealed the role of these genes in cellular processes such as cell proliferation, immune function, metabolism, and neurodegeneration, with high expression in muscle, heart, brain, adipose, and nerve tissues. Of the 52 traits tested, 23 showed significant genetic correlations with IC, and a higher genetic loading for IC was associated with higher IC scores.

conclusionsOverall, this study provides comprehensive evidence on the genetic architecture of IC, identifying novel genetic variants and biological pathways, advancing our current knowledge and laying the foundation for ongoing and future research on healthy aging.

Indexed as

Functional StatusGenetic LociHealthy AgingAdultAgedAged, 80 and overCanadaCanadian Longitudinal Study on AgingCell ProliferationDatasets as TopicFemaleGenome-Wide Association StudyHumansImmunityMaleMiddle AgedAging biomarkersFunctional abilityGWASHealthy agingIntrinsic capacity

Identifiers

PMID41066301
PMCPMC12510315

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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 OpenQuestion graph.