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

Genetic predisposition is a risk factor for office hypertension. We sought to determine whether genetic predisposition identifies individuals with ambulatory daytime hypertension. 1444 participants from the GAPP study (ages 25-41) were analyzed. We evaluated two measures of predisposition to hypertension: family history and polygenic risk scores (PRS). We evaluated correlation of predisposition with blood pressure traits and compared incremental value of each predisposition measure to a validated ambulatory BP prediction model. 12% of participants had office hypertension, while 37% had out-of-office hypertension. The correlation between 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 predicting ambulatory systolic blood pressure beyond a validated blood pressure prediction score (ΔAIC = -33), whereas family history does not (ΔAIC = 1). The difference between a baseline prediction algorithm for identifying ambulatory systolic 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 a white European sample from Liechtenstein, PRS provides incremental information in identification of individuals with ambulatory hypertension, unlike family history. However, these gains are modest and warrant further development to improve predictive utility at the point-of-care.