Kidney Function and Blood Pressure: A Bi-directional Mendelian Randomisation Study

AbstractObjectiveTo evaluate the bi-directional causal relation between kidney function and blood pressure.DesignMendelian randomisation study.SettingWe performed two-sample Mendelian randomisation analyses. Genetic instruments of kidney function traits were selected from summary statistics of genome-wide association studies (GWAS) of glomerular filtration rate estimated from serum creatinine (eGFRcr) and blood urea nitrogen (BUN) and were required to be associated with both eGFRcr and BUN to ensure that the instruments were more likely to represent the underlying kidney function. Genetic instruments of blood pressure were selected from summary statistics of GWAS of systolic and diastolic blood pressure. We investigated Mendelian randomisation hypothesis using several alternative approaches, including methods that are most robust to the presence of horizontal pleiotropy.ParticipantsThe summary statistics of eGFRcr included 567,460 participants from 54 cohorts, and the summary statistics of BUN included 243,031 participants from 48 cohorts from the Chronic Kidney Disease Genetics (CKDGen) Consortium. The summary statistics of systolic and diastolic blood pressure included 757,601 participants from the UK Biobank and 78 cohorts from the International Consortium for Blood Pressure (ICBP).ResultsSignificant evidence supported the causal effects of higher kidney function on lower blood pressure with multiple methods. Based on the mode-based Mendelian randomisation analysis approach, known for its robustness to the presence of pleiotropic effect, the effect estimate for 1 SD higher in eGFRcr was −0.17 SD unit (95 % CI: −0.09 to −0.24) in systolic blood pressure (SBP) and −0.15 SD unit (95% CI: −0.07 to −0.22) in diastolic blood pressure (DBP). In contrast, the causal effects of blood pressure on kidney function were not statistically significant.ConclusionsMendelian randomisation analyses support causal effects of higher kidney function on lower blood pressure. These results suggest preventing kidney function decline can reduce the public health burden of hypertension.

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Coping Strategies and Diastolic Blood Pressure

Psychological Reports ◽

10.2466/pr0.1989.65.2.443 ◽

1989 ◽

Vol 65 (2) ◽

pp. 443-449 ◽

Cited By ~ 12

Author(s):

Thomas A. Wright ◽

Dennis Sweeney

Keyword(s):

Blood Pressure ◽

Diastolic Blood Pressure ◽

Daily Living ◽

Phenomenological Analysis ◽

Stressful Events ◽

Lower Blood Pressure ◽

Service Employees ◽

Ways Of Coping ◽

Organizational Perspective ◽

Lower Blood

An organizational field study involving 95 civil service employees examined the ways these individuals coped with the stressful events of their daily living. Lazarus' cognitive-phenomenological analysis of psychological stress provided the theoretical framework. Subjects indicated on Lazarus' Ways of Coping Checklist those coping thoughts and actions used in the specific encounter described as stressful. As hypothesized, individuals experiencing higher diastolic blood pressure were more likely to cope using strategies characterized by wishful thinking, avoidance, and minimization of threat than were individuals exhibiting lower blood pressure. Implications from both an individual and organizational perspective are discussed.

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Trans-ethnic genome-wide association study of kidney function provides novel insight into effector genes and causal effects on kidney-specific disease aetiologies

10.1101/420273 ◽

2018 ◽

Author(s):

Andrew P Morris ◽

Thu H Le ◽

Haojia Wu ◽

Artur Akbarov ◽

Peter J van der Most ◽

...

Keyword(s):

Kidney Function ◽

Molecular Mechanisms ◽

Association Studies ◽

Causal Effects ◽

Genome Wide Association ◽

Mendelian Randomisation ◽

Genome Wide Association Studies ◽

Effector Genes ◽

Genome Wide ◽

Insight Into

Chronic kidney disease (CKD) affects ∼10% of the global population, with considerable ethnic differences in prevalence and aetiology. We assembled genome-wide association studies (GWAS)1-3 of estimated glomerular filtration rate (eGFR), a measure of kidney function that defines CKD, in 312,468 individuals from four ancestry groups. We identified 93 loci (20 novel), which were delineated to 127 distinct association signals. These signals were homogenous across ancestries, and were enriched for protein-coding exons, kidney-specific histone modifications, and transcription factor binding sites for HDAC2 and EZH2. Fine-mapping revealed 40 high-confidence variants driving eGFR associations and highlighted potential causal genes with cell-type specific expression in glomerulus, and proximal and distal nephron. Mendelian randomisation (MR) supported causal effects of eGFR on overall and cause-specific CKD, kidney stone formation, diastolic blood pressure (DBP) and hypertension. These results define novel molecular mechanisms and effector genes for eGFR, offering insight into clinical outcomes and routes to CKD treatment development.

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