ArticlePloS one2018
Frailty Index associates with GRIN2B in two representative samples from the United States and the United Kingdom.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- The phenotypic and genotypic association of grip strength with frailty, physical performance and functional limitations over time in older adults.Age and ageing · 2023Pooled it
- Article
- Frailty and genetics: linking molecular aging to clinical vulnerability.The journals of gerontology. Series A, Biological sciences and medical sciences · 2026Review
- Physiological health Age (PhysAge): a novel multi-system molecular timepiece predicts health and mortality in older adults.GeroScience · 2026Article
- Genome-wide association study of frailty and integrative functional analysis to elucidate its relationship with aging.GeroScience · 2026Article
- A multi-omics investigation of sarcopenia and frailty: Integrating genomic, epigenomic and telomere length data.Experimental physiology · 2025Article
- Multi-Polygenic prediction of Frailty and its Trajectories highlights Chronic Pain, Rheumatoid Arthritis, and Educational Attainment pathways.medRxiv : the preprint server for health sciences · 2025Article
- Utilizing multimodal approach to identify candidate pathways and biomarkers and predicting frailty syndrome in individuals from UK Biobank.GeroScience · 2024Article
- To Be Frail or Not to Be Frail: This Is the Question-A Critical Narrative Review of Frailty.Journal of clinical medicine · 2024Review
- Assessment of the bidirectional causal association between frailty and depression: A Mendelian randomization study.Journal of cachexia, sarcopenia and muscle · 2023Article
- University of Southern California and buck institute nathan shock center: multidimensional models of aging.GeroScience · 2021Article
- A genome-wide association study of the frailty index highlights brain pathways in ageing.Aging cell · 2021Article
- The degree of frailty as a translational measure of health in aging.Nature aging · 2021Review
- Genetics of frailty: A longevity perspective.Translational research : the journal of laboratory and clinical medicine · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The concept of frailty has been used in the clinical and research field for more than two decades. It is usually described as a clinical state of heightened vulnerability to poor resolution of homeostasis after a stressor event, which thereby increases the risk of adverse outcomes, including falls, delirium, disability and mortality. Here we report the results of the first genome-wide association scan and comparative gene ontology analyses where we aimed to identify genes and pathways associated with the deficit model of frailty. We used a discovery-replication design with two independent, nationally representative samples of older adults. The square-root transformed Frailty Index (FI) was the outcome variable, and age and sex were included as covariates. We report one hit exceeding genome-wide significance: the rs6765037 A allele was significantly associated with a decrease in the square-root transformed FI score in the Discovery sample (beta = -0.01958, p = 2.14E-08), without confirmation in the Replication sample. We also report a nominal replication: the rs7134291 A allele was significantly associated with a decrease in the square-root transformed FI score (Discovery sample: beta = -0.01021, p = 1.85E-06, Replication sample: beta = -0.005013, p = 0.03433). These hits represent the KBTBD12 and the GRIN2B genes, respectively. Comparative gene ontology analysis identified the pathways 'Neuropathic pain signalling in dorsal horn neurons' and the 'GPCR-Mediated Nutrient Sensing in Enteroendocrine Cells', exceeding the p = 0.01 significance in both samples, although this result does not survive correction for multiple testing. Considering the crucial role of GRIN2B in brain development, synaptic plasticity and cognition, this gene appears to be a potential candidate to play a role in frailty. In conclusion, we conducted genome-wide association scan and pathway analyses and have identified genes and pathways with potential roles in frailty. However, frailty is a complex condition. Therefore, further research is required to confirm our results and more thoroughly identify relevant biological mechanisms.
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