BACKGROUND:Hypertension is a key risk factor for major adverse cardiovascular events but remains difficult to treat in many individuals. Dietary interventions are an effective approach to lower blood pressure (BP) but are not equally effective across all individuals. BP is heritable, and genetics may be a useful tool to overcome treatment response heterogeneity. We investigated whether the genetics of BP could be used to identify individuals with hypertension who may receive a particular benefit from lowering sodium intake and boosting potassium levels.METHODS:In this observational genetic study, we leveraged cross-sectional data from up to 296 475 genotyped individuals drawn from the UK Biobank cohort for whom BP and urinary electrolytes (sodium and potassium), biomarkers of sodium and potassium intake, were measured. Biologically directed genetic scores for BP were constructed specifically among pathways related to sodium and potassium biology (pharmagenic enrichment scores), as well as unannotated genome-wide scores (conventional polygenic scores). We then tested whether there was a gene-by-environment interaction between urinary electrolytes and these genetic scores on BP.RESULTS:Genetic risk and urinary electrolytes both independently correlated with BP. However, urinary sodium was associated with a larger BP increase among individuals with higher genetic risk in sodium- and potassium-related pathways than in those with comparatively lower genetic risk. For example, each SD in urinary sodium was associated with a 1.47–mm Hg increase in systolic BP for those in the top 10% of the distribution of genetic risk in sodium and potassium transport pathways versus a 0.97–mm Hg systolic BP increase in the lowest 10% (P=1.95×10⁻³). This interaction with urinary sodium remained when considering estimated glomerular filtration rate and indexing sodium to urinary creatinine. There was no strong evidence of an interaction between urinary sodium and a standard genome-wide polygenic score of BP.CONCLUSIONS:The data suggest that genetic risk in sodium and potassium pathways could be used in a precision medicine model to direct interventions more specifically in the management of hypertension. Intervention studies are warranted.

中文翻译：

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利用遗传学来指导与高血压中钠和钾相关的干预措施

背景：高血压是主要不良心血管事件的关键危险因素，但对许多人来说仍然难以治疗。饮食干预是降低血压 (BP) 的有效方法，但并非对所有个体都同样有效。血压是可遗传的，遗传学可能是克服治疗反应异质性的有用工具。我们研究了 BP 遗传学是否可用于识别高血压患者，这些患者可能会从降低钠摄入量和提高钾水平中获得特别的益处。 方法：在这项观察性遗传学研究中，我们利用了来自多达 296 475 名基因型患者的横断面数据对来自英国生物银行队列的个体进行了血压和尿电解质（钠和钾）（钠和钾摄入量的生物标志物）的测量。 BP 的生物学定向遗传评分是专门在与钠和钾生物学相关的途径（药理学富集评分）以及未注释的全基因组评分（传统多基因评分）中构建的。然后我们测试了尿电解质与血压遗传评分之间是否存在基因与环境的相互作用。结果：遗传风险和尿电解质均与血压独立相关。然而，钠和钾相关途径遗传风险较高的个体与遗传风险相对较低的个体相比，尿钠与血压升高幅度更大相关。例如，对于钠和钾转运途径中遗传风险分布前 10% 的人来说，尿钠的每一个 SD 都与收缩压增加 1.47 毫米汞柱相关，而在尿钠转运途径中，排在前 10% 的人的收缩压则增加 0.97 毫米汞柱。最低10%（P =1.95×10 ^-3）。当考虑估计的肾小球滤过率并将钠与尿肌酐进行索引时，这种与尿钠的相互作用仍然存在。没有强有力的证据表明尿钠与 BP 标准全基因组多基因评分之间存在相互作用。结论：数据表明，钠和钾途径中的遗传风险可用于精准医学模型，以更具体地指导干预措施高血压的管理。干预研究是有必要的。