Research Paper Volume 15, Issue 24 pp 14985—14995

Does enhanced cognitive performance reduce fracture risk? a Mendelian randomization study

Shaoting Luo1, , Linfang Deng2, , Yufan Chen1, , Weizheng Zhou1, , Federico Canavese3, , Lianyong Li1, ,

  • 1 Department of Pediatric Orthopedics, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, P.R. China
  • 2 Department of Nursing, Jinzhou Medical University, Jinzhou 121001, Liaoning, P.R. China
  • 3 Department of Pediatric Orthopedic Surgery, Lille University Centre, Jeanne de Flandre Hospital, Lille 59000, Nord Department, France

Received: July 25, 2023       Accepted: November 3, 2023       Published: December 18, 2023      

https://doi.org/10.18632/aging.205325
How to Cite

Copyright: © 2023 Luo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Objective: While observational studies have suggested a link between cognitive performance and fracture risk, the causality and site-specific nature are unclear. We applied Mendelian randomization (MR) to elucidate these associations.

Methods: 147 single-nucleotide polymorphisms (SNPs) tied strongly to cognitive performance (p< 5e-8) were selected. We performed MR analysis to investigate the causal relationship between cognitive performance and fractures at specific sites, including the wrist, upper arm, shoulder, ribs, sternum, thoracic spine, lumbar spine, pelvis, femur, leg, and ankle. The primary estimate was determined using the inverse variance-weighted method. Additionally, we examined heterogeneity using the MR Pleiotropy RESidual Sum Outlier test and Cochran Q, and employed MR-Egger regression to identify horizontal pleiotropy.

Results: MR analysis identified a causal association between cognitive performance and fractures at the lumbar-spine-pelvis (odds ratio [OR] = 0.727, 95% CI = 0.552–0.956, p = 0.023), and ribs-sternum-thoracic spine sites (OR = 0.774, 95% CI = 0.615–0.974, p = 0.029). However, no causal association was found for fractures at other sites.

Conclusions: This study provided evidence of a causal connection between cognitive performance and fracture risk at certain locations. These findings underline the potential of cognitive enhancement strategies as innovative and effective methods for fracture prevention.

Abbreviations

MR: Mendelian Randomization; IVs: instrumental variables; GWASs: genome-wide association studies; IVW: inverse-variance weighted; MR-PRESSO: Mendelian Randomization Pleiotropy RESidual Sum and Outlier; SNPs: single nucleotide polymorphisms; COGENT: Cognitive Genomics Consortium; Cis: confidence intervals.