Genetic predisposition to high blood pressure and out-of-office hypertension: insights from a population sample in Liechtenstein

Abstract Genetic predisposition is a risk factor for office hypertension. We tested whether genetic background could identify individuals with ambulatory daytime hypertension in a sample of white Europeans from Liechtenstein. We evaluated two measures of predisposition to hypertension: family history and polygenic risk scores (PRS). Our analytic sample contained 1444 participants aged 25 to 41. 12% of participants had office hypertension, while 37% had out-of-office hypertension. The correlation between blood pressure PRS and family history of hypertension was low (R2 = 4.96x10-3), but both were strongly associated with ambulatory blood pressure (2.2 mmHg per 1 SD increase [95% CI: 1.6, 2.7] & 2.4 mmHg increase with positive family history [95% CI: 1.3, 3.4], respectively). PRS provides incremental improvement in predicting ambulatory systolic blood pressure beyond a validated blood pressure prediction algorithm (ΔAIC = -33), whereas family history does not (ΔAIC = 1). The difference in performance between a baseline algorithm for identifying ambulatory systolic daytime hypertension (positive likelihood ratio of 6.87 [95% CI: 5.56, 8.49]; negative likelihood ratio of 0.45 [95% CI: 0.39, 0.51]) and the same model with PRS integrated (positive likelihood ratio of 7.69 [95% CI: 6.18, 9.57]; negative likelihood ratio of 0.43 [95% CI: 0.37, 0.49]) was modest. In conclusion, in a European sample from Liechtenstein, PRS and family history represent distinct constructs associated with ambulatory blood pressure. Unlike family history, polygenic risk scores provide incremental information identifying individuals with ambulatory hypertension. However, these gains are modest and warrant further development to improve performance at the point-of-care.