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Post-traumatic stress disorder and REM-sleep behavior disorder: exploring genetic associations and causal links
Preprint   Open access

Post-traumatic stress disorder and REM-sleep behavior disorder: exploring genetic associations and causal links

Morvarid Ghamgosar Shahkhali, Lee E. Neilson, Lang Liu, Mohammad H. Ghamgosar Shahkhali, Eric Yu, Farnaz Asayesh, Jamil Ahmad, Meron Teferra, Isabelle Arnulf, Pauline Dodet, …
medRxiv
Cold Spring Harbor Laboratory Press, 1.1
09/08/2025
DOI: 10.1101/2025.09.05.25335205
PMCID: PMC12440045
PMID: 40963755
url
https://doi.org/10.1101/2025.09.05.25335205View
Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

To explore potential genetic and/or causal associations between Post-Traumatic Stress Disorder and neurodegeneration-related isolated/idiopathic rapid-eye-movement sleep behavior disorder. We conducted polygenic risk score, genetic correlation, and Mendelian randomization analyses using the latest genome-wide association studies summary statistics and individual genotyping data. Next, a blinded observer examined dopamine transporter imaging binding status—a marker of neurodegeneration—in patients with isolated/idiopathic rapid-eye movement sleep behavior disorder, with (N = 6) and without Post-Traumatic Stress Disorder (N = 32). Polygenic risk scores for Post-Traumatic Stress Disorder were associated with isolated/idiopathic rapid-eye-movement sleep behavior disorder, with each standard deviation increase linked to 14.7% higher odds (odds ratio = 1.15, 95% confidence interval: 1.04 to 1.26, p = 0.005). However, genetic correlation was weak, and Mendelian randomization did not support a potential causal relationship. The proportion of individuals with abnormal dopamine transporter imaging binding status was significantly higher in the Post-Traumatic Stress Disorder group compared to those without the disorder (p=0.01, X2 = 6.62). Polygenic risk scores analysis identified an association between Post-Traumatic Stress Disorder and neurodegeneration-related isolated/idiopathic rapid-eye-movement sleep behavior disorder, consistent with the result from the small exploratory substudy. The lack of strong genetic correlation or causation may reflect limited sample size. Further research with larger and more diverse cohorts is crucial to clarify the genetic, biological and physiological mechanisms underlying this association.
 Genetic and Genomic Medicine

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