Department of Medicine, University of Verona, Verona, Italy (A.G., P.M., C.F.).
Department of Clinical Sciences, Clinical Research Center, Lund University, Malmö, Sweden (A.G., M.S., C.F., O.M.).
Hypertension. 2021 Jan;77(1):169-177. doi: 10.1161/HYPERTENSIONAHA.120.15449. Epub 2020 Nov 23.
The clinical value of the polygenetic component of blood pressure (BP) is commonly questioned. We evaluated a genetic risk score for BP (BP-GRS), based on the most recently published genome-wide association studies variants that were significantly associated with either systolic BP or diastolic BP, for prediction of hypertension and cardiovascular end points. The genotyping was performed in 2 urban-based prospective cohorts: the Malmö Diet and Cancer (n=29 295) and the Malmö Preventive Project (n=9367) and a weighted BP-GRS based on 858 SNPs was calculated. At baseline, we found a difference of 9.0 mm Hg (systolic BP) and 4.8 mm Hg (diastolic BP) between the top and the bottom quartile of BP-GRS. In Malmö Preventive Project, the top versus bottom quartile of BP-GRS was associated with a doubled risk of incident hypertension (odds ratio, 2.05 [95% CI, 1.75-2.39], =1.4×10), a risk higher than that of body mass index, as evaluated in quartiles. In Malmö Diet and Cancer, significant association was found between the age and sex-adjusted BP-GRS and the incidence of total cardiovascular events, stroke, coronary artery disease, heart failure, atrial fibrillation, and total mortality. Most of these associations remained significant after adjusting for traditional risk factors, including hypertension. BP-GRS could contribute predictive information regarding future hypertension, with an effect size comparable to other well-known risk factors such as obesity, and predicts cardiovascular events. Given that the exposure to high polygenetic risk starts at birth, we suggest that the BP-GRS might be useful to identify children or adolescents who would benefit from early hypertension screening and treatment.
血压的多基因成分的临床价值通常受到质疑。我们评估了一种基于与收缩压或舒张压显著相关的最新全基因组关联研究变异的血压遗传风险评分(BP-GRS),用于预测高血压和心血管终点。基因分型在两个基于城市的前瞻性队列中进行:马尔默饮食与癌症(n=29295)和马尔默预防项目(n=9367),并根据 858 个 SNP 计算加权 BP-GRS。在基线时,我们发现 BP-GRS 最高和最低四分位数之间的收缩压差异为 9.0mmHg,舒张压差异为 4.8mmHg。在马尔默预防项目中,BP-GRS 最高与最低四分位数与高血压发病风险增加两倍相关(优势比,2.05[95%CI,1.75-2.39],=1.4×10),风险高于按四分位数评估的体重指数。在马尔默饮食与癌症中,年龄和性别调整后的 BP-GRS 与总心血管事件、中风、冠状动脉疾病、心力衰竭、心房颤动和总死亡率的发生率之间存在显著相关性。在调整了传统危险因素(包括高血压)后,这些相关性中的大多数仍然显著。BP-GRS 可以提供有关未来高血压的预测信息,其效果大小与肥胖等其他知名危险因素相当,并可预测心血管事件。鉴于高多基因风险的暴露始于出生,我们建议 BP-GRS 可用于识别可能受益于早期高血压筛查和治疗的儿童或青少年。