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Decoding Causal Associations Between Neuropsychiatric Disorders and Rotator Cuff Tendinopathy: A Two-Sample Mendelian
Weizhe Zhang1, Ming Chen2, Haozhang Huang3
1Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Sun Yat-Sen University, Guangzhou City, Guangdong Province, China.
Brain and Behavior
|January 30, 2026
Summary
Genetic links between attention deficit/hyperactivity disorder (ADHD) and post-traumatic stress disorder (PTSD) increase rotator cuff tendinopathy (RCT) risk. Early screening and targeted prevention are recommended for these populations.
Area of Science:
- Orthopedics
- Psychiatry
- Genetics
Background:
- Rotator cuff tendinopathy (RCT) affects millions globally, necessitating effective treatment strategies.
- Neuropsychiatric disorders (ND) share underlying pathways with tendinopathy, but causal links remain unclear.
- Understanding genetic associations can inform personalized treatments and injury prevention for ND patients at risk of RCT.
Purpose of the Study:
- To investigate the genetic association between eight major neuropsychiatric disorders (ND) and rotator cuff tendinopathy (RCT).
- To establish potential causal relationships using a bidirectional two-sample Mendelian randomization (MR) approach.
- To identify specific ND that confer an increased genetic risk for developing RCT.
Main Methods:
- Utilized genome-wide association studies (GWAS) data for ADHD, ASD, BD, epilepsy, MDD, OCD, PTSD, SCZ, and RCT in European ancestry.
- Employed bidirectional two-sample Mendelian randomization (MR) analyses to assess causal links.
- Conducted sensitivity analyses (MR-Egger, weighted median, CAUSE) and multivariable MR adjusting for confounders.
Main Results:
- Genetic predisposition to ADHD and PTSD significantly increased RCT risk (OR 1.14 and 2.23, respectively).
- Major depressive disorder (MDD) showed a similar association, but it was attenuated after confounder adjustment.
- Multivariable MR confirmed ADHD and PTSD as robust causal factors for RCT, even after adjusting for lifestyle and socioeconomic factors.
Conclusions:
- Attention deficit/hyperactivity disorder (ADHD) and post-traumatic stress disorder (PTSD) are genetically associated with an increased risk of rotator cuff tendinopathy (RCT).
- Findings highlight the need for early screening and targeted overuse injury prevention in individuals with ADHD and PTSD.
- Specialized clinical interventions may help alleviate the RCT burden in these at-risk populations.
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