GWAS for urinary sodium and potassium excretion highlights pathways shared with cardiovascular traits
GWAS for urinary sodium and potassium excretion highlights pathways shared with cardiovascular traits
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DOI：
10.1038/s41467-019-11451-y
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发表时间：
2019-08
影响因子：
16.6
通讯作者：
R. Pazoki;E. Evangelou;D. Mosén-Ansorena;R. Pinto;I. Karaman;Paul Blakeley;D. Gill;V. Zuber;P. Elliott;I. Tzoulaki;A. Dehghan
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文献类型：
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作者：
R. Pazoki;E. Evangelou;D. Mosén-Ansorena;R. Pinto;I. Karaman;Paul Blakeley;D. Gill;V. Zuber;P. Elliott;I. Tzoulaki;A. Dehghan
尿钠和尿钾排泄与血压（BP）和心血管疾病（CVD）有关。这些特征之间确切的生物学联系还有待阐明。在此，我们利用来自英国生物银行研究的446,237名欧洲血统个体的数据，在一项大规模尿钠和尿钾排泄全基因组关联研究（GWAS）中确定了50个钠和13个钾排泄位点。我们使用孟德尔随机化、功能评估、共定位、遗传风险评分和途径分析等多种分析方法对结果进行了广泛的询问。我们确定了尿钠和钾表达与心血管特征之间的共同遗传成分。独创性途径分析表明，尿钠和钾排泄位点在对刺激的行为反应中被过度代表。我们的研究强调了尿钠和钾排泄与心血管特征之间的共同途径。
Urinary sodium and potassium excretion are associated with blood pressure (BP) and cardiovascular disease (CVD). The exact biological link between these traits is yet to be elucidated. Here, we identify 50 loci for sodium and 13 for potassium excretion in a large-scale genome-wide association study (GWAS) on urinary sodium and potassium excretion using data from 446,237 individuals of European descent from the UK Biobank study. We extensively interrogate the results using multiple analyses such as Mendelian randomization, functional assessment, co localization, genetic risk score, and pathway analyses. We identify a shared genetic component between urinary sodium and potassium expression and cardiovascular traits. Ingenuity pathway analysis shows that urinary sodium and potassium excretion loci are over-represented in behavioural response to stimuli. Our study highlights pathways that are shared between urinary sodium and potassium excretion and cardiovascular traits.