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GWAS 分析尿钠和尿钾排泄与心血管特征的共享途径。

GWAS for urinary sodium and potassium excretion highlights pathways shared with cardiovascular traits.

机构信息

MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, St Mary's campus, Norfolk Place, London, W2 1PG, UK.

Department of Hygiene and Epidemiology, University of Ioannina Medical School, 45110, Ioannina, Greece.

出版信息

Nat Commun. 2019 Aug 13;10(1):3653. doi: 10.1038/s41467-019-11451-y.

Abstract

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.

摘要

尿钠和尿钾排泄与血压(BP)和心血管疾病(CVD)有关。这些特征之间的确切生物学联系尚待阐明。在这里,我们在 UK Biobank 研究中对 446,237 名欧洲血统的个体的尿钠和钾排泄进行了大规模全基因组关联研究(GWAS),鉴定出 50 个与钠排泄相关的位点和 13 个与钾排泄相关的位点。我们使用多种分析方法(如孟德尔随机化、功能评估、共定位、遗传风险评分和途径分析)对结果进行了广泛的研究。我们发现尿钠和尿钾表达与心血管特征之间存在共同的遗传成分。通路分析表明,尿钠和尿钾排泄与刺激的行为反应有关。我们的研究强调了尿钠和尿钾排泄与心血管特征之间共享的途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/272f/6692500/d1dccad9345a/41467_2019_11451_Fig1_HTML.jpg

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