Does blood pressure level matter more in individuals with higher genetic risk of dementia? A polygenic interaction study in the UK Biobank
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Background & Aims
The causal role of blood pressure (BP) in dementia remains debated. BP may act as an effect modifier; whereby elevated pressure accelerates cognitive decline in the presence of existing neurodegenerative or cerebrovascular pathology, through vascular injury and impaired cerebral homeostasis. We examine whether genetic liability to dementia interacts with BP to influence risk of dementia diagnosis.
Methods
In 334,759 UK Biobank participants, we calculated weighted polygenic risk scores (PRSs) for Alzheimer’s disease (AD), vascular dementia (VaD), white matter hyperintensity (WMH) volume (a neuroimaging marker of cerebral small vessel disease), systolic (SBP), and diastolic (DBP) blood pressure. Logistic regression models examined main effects of the BP PRSs on dementia outcomes, and tested interactions between genetic liability to dementia and SBP/DBP levels to see whether they affect risk of dementia diagnoses.
Results
The SBP PRS increased dementia risk across all subtypes: AD (OR = 1.04, 95%CI: 1.01–1.08), VaD (OR = 1.06, 95%CI: 1.00–1.11), and all-cause dementia (OR = 1.05, 95%CI: 1.03–1.08). The DBP PRS showed little evidence of association with any dementia outcome. There was little evidence of multiplicative interaction between BP and genetic liability to dementia. Associations of the SBP PRS with dementia risk were consistent across high and low dementia genetic liability groups. For example, for all-cause dementia, the SBP PRS showed similar associations across both high (OR = 1.05, 95% CI: 1.02–1.07) and low (OR = 1.05, 95% CI: 1.02–1.08) AD genetic liability groups (interaction P value = 0.467). Similarly, no strong evidence of interaction was observed between the DBP PRS and dementia genetic liability.
Conclusions
Our study supports elevated SBP as an independent risk factor for dementia across subtypes, with little evidence that this effect is modified by genetic predisposition to Alzheimer’s disease or vascular dementia. Our findings reinforce the importance of population-wide strategies to lower SBP as a means of reducing dementia risk at the population level.
