ArticleNature genetics2025
Uncovering the multivariate genetic architecture of frailty with genomic structural equation modeling.
Article in Nature genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Epigenetic Signatures of Frailty: A Systematic Review, Meta-Analysis, and Network Analysis of the Chemical Exposome.International journal of molecular sciences · 2026Pooled it
- A cross-ancestry genetic atlas of shared susceptibility between infectious diseases and cancer.Functional & integrative genomics · 2026Article
- Sugar rationing in the first 1000 days of life and risk of frailty: evidence from a natural experiment.The journal of nutrition, health & aging · 2026Article
- The association of frailty with age and lifespan in mice differs by strain and sex.The journals of gerontology. Series A, Biological sciences and medical sciences · 2026Article
- Shared genetic architecture of schizophrenia and Alzheimer's disease and related dementias implicates 16p11.2 and lifespan brain vulnerability.Molecular psychiatry · 2026Article
- Ultra-Fast Implementation of Multivariate GWAS in Genomic SEM Using Flexible Analytic Estimation.bioRxiv : the preprint server for biology · 2026Article
- Genome integrity, somatic mutation, and the N-of-1 imperative in aging research.Biogerontology · 2026Review
- Whole Genome Sequence Analysis of Weight Loss in 16 972 Participants With COPD Reveals Novel Risk Loci in DRAIC and RFX3.Journal of cachexia, sarcopenia and muscle · 2026Article
- Integrative genomic and spatial transcriptomic analysis elucidates the oligodendrocyte-mediated etiology of epileptic cortical thinning.Epilepsia open · 2026Article
- Plasma proteomics link menopause timing to brain aging and dementia risk.Research square · 2026Article
- Plasma proteomics link menopause timing to brain aging and dementia risk.medRxiv : the preprint server for health sciences · 2026Article
- Frailty and genetics: linking molecular aging to clinical vulnerability.The journals of gerontology. Series A, Biological sciences and medical sciences · 2026Review
- Electronic frailty index based on comprehensive geriatric assessment in primary care: feasibility, validity, and reliability.BMC geriatrics · 2026Article
- Genome-wide association study of frailty and integrative functional analysis to elucidate its relationship with aging.GeroScience · 2026Article
- Shared Genetic Liability across Systems of Psychiatric and Physical Illness.Nature communications · 2026Article
- Impact of anesthesia methods on adverse cardiovascular events during painless gastroscopy in frail older patients: study protocol for a prospective controlled trial.Frontiers in medicine · 2026Article
- Combining cross-sectional and longitudinal genomic approaches to identify determinants of cognitive and physical decline.Nature communications · 2025Article
- Examining the genetic relationship between Alzheimer's disease, schizophrenia and their shared risk factors using genomic structural equation modelling.Brain communications · 2025Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Frailty is a multifaceted clinical state associated with accelerated aging and adverse health outcomes. Informed etiological models of frailty hold promise for producing widespread health improvements across the aging population. Frailty is currently measured using aggregate scores, which obscure etiological pathways that are only relevant to subcomponents of frailty. Here we perform a multivariate genome-wide association study of the latent genetic architecture between 30 frailty deficits, which identifies 408 genomic risk loci. Our model includes a general factor of genetic overlap across all deficits, plus six new factors indexing a shared genetic signal across specific groups of deficits. We demonstrate the added clinical and etiological value of the six factors, including predicting frailty in external datasets, highlighting divergent genetic correlations with clinically relevant outcomes and uncovering unique underlying biology linked to aging. We show that nuanced models of frailty are key to understanding its causes and how it relates to worse health.
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Registered trials
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.