A 2016 study of 27,581 people over 65 found one variant on chromosome 8 genome-wide-significantly linked to grip strength — a widely used clinical marker of aging and frailty, not a disease itself.
Grip strength, measured with a handheld dynamometer, is one of the most widely used simple physical measures in aging research and geriatric medicine. It correlates with overall muscle strength and function, and declining grip strength is a well-established predictor of frailty, disability, and mortality risk in older adults — which is why researchers have looked for the genetic factors behind why grip strength varies and declines differently between people.
Matteini et al. 2016, working within the CHARGE consortium, measured grip strength in 27,581 people of European descent over age 65, across 14 cohort studies, and analyzed roughly 2,700,000 genotyped and imputed variants. The discovery meta-analysis found 2 genome-wide-significant and 39 suggestive associations; after combining with a 6,393-person replication sample, one locus held up at genome-wide significance: rs752045 on chromosome 8 (beta 0.47 kg per copy of the associated allele, p=5.2×10⁻¹⁰).
The paper describes rs752045 as sitting in an intergenic region that is nonetheless functionally active in skeletal muscle: it falls within an accessible-chromatin region in muscle cells (myotubes) and alters a binding site for CEBPB, a transcription factor already implicated in muscle repair. This site's own gene field maps the variant to the nearest named gene, CSMD1, by distance — a naming convention, not a claim that CSMD1 itself is the functional gene the paper's own mechanism points to.
A separate analysis of lower-body strength, in a subset of the same cohorts, found no genome-wide-significant loci — grip strength and lower-body strength do not necessarily share the same genetic architecture, at least at the sample sizes available in this study.
Positions joined since this page was written
What this is The text above discusses the variants this page was written around. Since then the catalogue has joined 2 more positions to it, by shared trait or shared paper. They are listed here by the paper each came from; the text does not describe them, and each variant page carries that study's own record.
Schoeler T et al. 2025, Nature communications rs150330307 (CASQ1) — PMID:40374629
Jones G et al. 2021, Nature communications rs2899611 (ALDH1A2) — PMID:33510174
2026-01-27 · Genome-wide association and integrative analyses of relative handgrip strength identify polygenic determinants of gastrointestinal disorder susceptibility. BMC Gastroenterology. 2026. DOI:10.1186/s12876-026-04624-9
Hand grip strength (adjusted for BMI as relative hand grip strength, RHGS) is a marker of skeletal muscle quality, and this UK Biobank study of 405,394 Europeans set out to test whether it has a genuine causal relationship with digestive disorders, not just a correlation via general frailty. The GWAS itself found 1,111 independent SNPs across 226 loci and 407 genes; transcriptome-wide association prioritized L3MBTL3, CEP192 and NUCKS1, highly expressed in muscle cell types. The more clinically interesting results came from Mendelian randomization: genetically higher RHGS reduced the odds of diaphragmatic hernia (OR=0.45), diverticular intestine disease (OR=0.42), NAFLD (OR=0.49) and peptic ulcer (OR=0.54) -- a one-directional causal signal, not merely correlation. A polygenic risk score for RHGS replicated smaller but consistent protective associations with abdominal hernia, diaphragmatic hernia and diverticular disease. Notably, the protective effect was weakened by diabetes, high cholesterol and smoking, but strengthened by a cardioprotective diet and higher fiber intake -- muscle strength's protective effect on the gut is modifiable by lifestyle, not fixed. This site's hand grip strength page carries 59 variants; none of L3MBTL3, CEP192 or NUCKS1 are currently among them, and this is also a genuine new connection to the diverticular disease and peptic ulcer disease pages this site already has.
Grip strength is a physical measurement, not a diagnosis, and this page's variants do not predict an individual's strength or frailty risk. The one genome-wide-significant locus here has a small effect (under 0.5 kg per allele copy) on a trait shaped overwhelmingly by age, sex, body size, activity level, and overall health.
Clinically, grip strength is measured directly with a dynamometer as part of frailty and sarcopenia assessments — there is no role for genetic testing in that evaluation, and nothing here changes how grip strength is measured or interpreted in a clinical setting.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Hand Grip Strength comes down to these specific, well-studied positions — not a diagnosis. 61 positions are linked to this page; the ones this page's own text discusses are shown first.
The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 59 of 61 linked studies with a resolved discovery ancestry.
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Hand Grip Strength. MyGeneLog™. https://www.mygenelog.com/conditions/hand-grip-strength
Grip strength, measured with a handheld dynamometer, is a widely used marker of overall muscle strength and function. Declining grip strength predicts frailty, disability, and mortality risk in older adults, which is why researchers look for genetic factors behind it.
Studying 27,581 people of European descent over age 65, it found one variant, rs752045 on chromosome 8, genome-wide-significantly associated with grip strength (beta 0.47 kg per allele copy, p=5.2×10⁻¹⁰), after combining the discovery analysis with a 6,393-person replication sample.
No. The effect size is small — under 0.5 kg per allele copy — on a trait shaped mostly by age, sex, body size, activity level, and overall health. It is a population-level statistical finding, not an individual prediction.
The paper found rs752045 alters a binding site for CEBPB, a transcription factor involved in muscle repair, in an otherwise intergenic region. This site's catalogue maps the variant to the nearest named gene, CSMD1, by distance — a labeling convention, not a claim that CSMD1 itself is the functional gene.
Free to reuse. This page's text is original writing from freely-available research, licensed CC BY 4.0 — reuse it, including commercially, with attribution to MyGeneLog™. It's general research-derived information, not medical advice or a diagnosis — see Terms of Use.