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Cortical Morphology and Susceptibility to Fall-Related Fractures: A Bidirectional Mendelian Randomization Study.

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Title: Cortical Morphology and Susceptibility to Fall-Related Fractures: A Bidirectional Mendelian Randomization Study.
Authors: Yang XL; Department of Nursing, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China., Zhao QH; Department of Nursing, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China., Xiao MZ; Department of Nursing, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China., Ma YZ; Department of Nursing, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China., Hong YM; Department of Nursing, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Source: Geriatrics & gerontology international [Geriatr Gerontol Int] 2026 Oct; Vol. 26 (10), pp. e70839.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Japan Geriatrics Society Country of Publication: Japan NLM ID: 101135738 Publication Model: Print Cited Medium: Internet ISSN: 1447-0594 (Electronic) Linking ISSN: 14470594 NLM ISO Abbreviation: Geriatr Gerontol Int Subsets: MEDLINE
Imprint Name(s): Original Publication: [Tokyo, Japan] : Carlton, Vic., Australia : Japan Geriatrics Society ; Blackwell Science, c2001-
MeSH Terms: Accidental Falls*/statistics & numerical data , Fractures, Bone*/etiology , Fractures, Bone*/epidemiology , Fractures, Bone*/genetics , Mendelian Randomization Analysis*, Humans ; Bone Density ; Female ; Male ; Polymorphism, Single Nucleotide ; Genome-Wide Association Study
Abstract: Aim: Injurious falls and low-energy fractures after a simple fall cause substantial morbidity in older adults; observational brain-structure associations are vulnerable to confounding and reverse causation. To test whether predicted regional cortical thickness or surface area causally influences falls and fractures after a simple fall, and to evaluate reverse causality.
Methods: Bidirectional two-sample Mendelian randomization used cortical morphology across 34 regions (> 51 000 Europeans). Outcomes were falls/tendency to fall and simple-fall fractures. Independent genome-wide significant instruments (p < 5 × 10-8) were clumped at r2 = 0.001 within a 10 000 kb window, retained if SNP-level F statistics were > 10, and analyzed using inverse-variance weighted MR with sensitivity methods, pleiotropy/directionality checks, and Benjamini-Hochberg FDR correction. Estimated bone mineral density (eBMD) was explored as a potential mediator.
Results: After FDR correction and pleiotropy screening, larger caudal anterior cingulate surface area was associated with lower odds of fracture resulting from a simple fall (OR 0.95, 95% CI 0.92-0.98; pFDR = 0.0159), whereas larger insula surface area was related to higher odds of fracture resulting from a simple fall (OR 1.05, 95% CI 1.02-1.08; pFDR = 0.0037). Associations with the broader falls/tendency-to-fall phenotype were not robust. Reverse MR showed no evidence that falls or simple-fall fractures altered cortical traits, and exploratory eBMD analyses did not support mediation.
Conclusions: Genetically predicted surface area in the caudal anterior cingulate and insula was associated with susceptibility to fractures resulting from simple falls. These findings require replication and functional validation before specific neurobiological mechanisms or clinical applications can be inferred.
(© 2026 Japan Geriatrics Society.)
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Grant Information: 24SKGH040 Chongqing Municipal Education Commission Humanities and Social Sciences Research Project; HLPY2025-12 First Affiliated Hospital of Chongqing Medical University's 2025 Nursing Scientific Research and Innovation Project; CYYY-DSTDXM-202409 2024 Hospital-level Graduate Supervisor Team Project of the First Clinical College of Chongqing Medical University
Contributed Indexing: Keywords: cortical morphology; falls; fall‐related fractures; mendelian randomization; surface area
Entry Date(s): Date Created: 20260930 Date Completed: 20260930 Latest Revision: 20260930
Update Code: 20260930
DOI: 10.1111/ggi.70839
PMID: 42813465
Database: MEDLINE
Description
ISSN:1447-0594
DOI:10.1111/ggi.70839