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Genetic predisposition and brain structural damage mediate the link between alcohol intake and acute cerebrovascular events: a prospective cohort study

cardiology
neurology
nutrition
radiology-and-medical-imaging
medical-genetics

Abstract

Background.
Although alcohol has been implicated in risk of acute cerebrovascular diseases (ACDs), little is known about how genetic predisposition and brain structural alterations contribute to this relationship. This study aimed to investigate the underlying mechanisms driven by genetic risk and brain structures.
Methods.
A total of 299964 participants from the UK Biobank were included in the m ultivariate Cox regression to examine the longitudinal association of alcohol and ACDs. The synergistic effect of alcohol and genetic factors was further explored by Cox analysis incorporating polygenic risk scores (PRS). Mediation analysis was further performed to explore the potential effects of brain structures in the association between alcohol and ACD s risk.
Results.
During a mean follow-up time of around 14 years, 8655 incident cases of ACDs were documented . Alcohol intake mainly drove ischemic events. For every standard deviation (SD) increase in alcohol intake, there was a 7% increase in the risk ofischemic stroke (Hazard Ratio [HR]=1.07). Individuals exposed to low or increasing levels of alcohol (females: ≤35 units/week; males: ≤50 units/week ) exhibited a 20% decreased risk of ACDs compared to those exposed to higher levels of alcohol (Both HRs=0.80, Both P <0.001). PRS indicated a synergistic effect between alcohol consumption and genetic risk factors in developing ACDs. Atrophy of the right putamen and damage to right superior thalamic radiation played a mediating role.
Conclusion.
The potential importance of early brain structure monitoring and alcohol intervention for individuals with high genetic risk was emphasized.
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