scholarly journals Plasma Proteomics of Renal Function: A Trans-ethnic Meta-analysis and Mendelian Randomization Study

2021 ◽  
pp. ASN.2020071070
Author(s):  
Pamela Matías-García ◽  
Rory Wilson ◽  
Qi Guo ◽  
Shaza Zaghlool ◽  
James Eales ◽  
...  
Keyword(s):  
Renal Function ◽  
Plasma Proteins ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Meta Analysis ◽  
Kidney Tissue ◽  
Renal Tissue ◽  
Cross Sectional Study ◽  
Causal Relationships ◽  
Cross Sectional

Background: Studies on the relationship between renal function and the human plasma proteome have identified several potential biomarkers. However, investigations have been conducted largely in European populations, and causality of the associations between plasma proteins and kidney function has never been addressed. Methods: A cross-sectional study of 993 plasma proteins among 2,882 participants in four studies of European and admixed ancestries (KORA, INTERVAL, HUNT, QMDiab) identified trans-ethnic associations between eGFR/CKD and proteomic biomarkers. For the replicated associations, two-sample bidirectional Mendelian randomization (MR) was used to investigate potential causal relationships. Publicly available datasets and transcriptomic data from independent studies were used to examine the association between gene expression in kidney tissue and eGFR . Results: Fifty-seven plasma proteins were associated with eGFR, including one novel protein. Twenty-three of these were additionally associated with CKD. The strongest inferred causal effect was the positive effect of eGFR on testican-2, in line with the known biological role of this protein and the expression of its protein-coding gene (SPOCK2) in renal tissue. We also observed suggestive evidence of an effect of melanoma inhibitory activity (MIA), carbonic anhydrase III, and cystatin-M on eGFR. Conclusions: In a discovery-replication setting, we identified 57 proteins trans-ethnically associated with eGFR. The revealed causal relationships are an important stepping-stone in establishing testican-2 as a clinically relevant physiological marker of kidney disease progression, and point to additional proteins warranting further investigation.

scholarly journals Causal effect of renal function on venous thromboembolism: a two-sample Mendelian randomization investigation

2021 ◽  
Author(s):  
Shuai Yuan ◽  
Maria Bruzelius ◽  
Susanna C. Larsson
Keyword(s):  
Renal Function ◽  
Venous Thromboembolism ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Meta Analysis ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
Genome Wide ◽  
Increased Risk ◽  
Mr Study

AbstractWhether renal function is causally associated with venous thromboembolism (VTE) is not yet fully elucidated. We conducted a two-sample Mendelian randomization (MR) study to determine the causal effect of renal function, measured as estimated glomerular filtration rate (eGFR), on VTE. Single-nucleotide polymorphisms associated with eGFR were selected as instrumental variables at the genome-wide significance level (p < 5 × 10−8) from a meta-analysis of 122 genome-wide association studies including up to 1,046,070 individuals. Summary-level data for VTE were obtained from the FinnGen consortium (6913 VTE cases and 169,986 non-cases) and UK Biobank study (4620 VTE cases and 356,574 non-cases). MR estimates were calculated using the random-effects inverse-variance weighted method and combined using fixed-effects meta-analysis. Genetically predicted decreased eGFR was significantly associated with an increased risk of VTE in both FinnGen and UK Biobank. For one-unit decrease in log-transformed eGFR, the odds ratios of VTE were 2.93 (95% confidence interval (CI) 1.25, 6.84) and 4.46 (95% CI 1.59, 12.5) when using data from FinnGen and UK Biobank, respectively. The combined odds ratio was 3.47 (95% CI 1.80, 6.68). Results were consistent in all sensitivity analyses and no horizontal pleiotropy was detected. This MR-study supported a casual role of impaired renal function in VTE.

scholarly journals Using a Two-Sample Mendelian Randomization Method in Assessing the Causal Relationships Between Human Blood Metabolites and Heart Failure

2021 ◽  
Vol 8 ◽  
Author(s):  
Zixian Wang ◽  
Shiyu Chen ◽  
Qian Zhu ◽  
Yonglin Wu ◽  
Guifeng Xu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Human Blood ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Blood Metabolites ◽  
Causal Relationships

Background: Heart failure (HF) is the main cause of morbidity and mortality worldwide, and metabolic dysfunction is an important factor related to HF pathogenesis and development. However, the causal effect of blood metabolites on HF remains unclear.Objectives: Our chief aim is to investigate the causal relationships between human blood metabolites and HF risk.Methods: We used an unbiased two-sample Mendelian randomization (MR) approach to assess the causal relationships between 486 human blood metabolites and HF risk. Exposure information was obtained from Sample 1, which is the largest metabolome-based genome-wide association study (mGWAS) data containing 7,824 Europeans. Outcome information was obtained from Sample 2, which is based on the results of a large-scale GWAS meta-analysis of HF and contains 47,309 cases and 930,014 controls of Europeans. The inverse variance weighted (IVW) model was used as the primary two-sample MR analysis method and followed the sensitivity analyses, including heterogeneity test, horizontal pleiotropy test, and leave-one-out analysis.Results: We observed that 11 known metabolites were potentially related to the risk of HF after using the IVW method (P &lt; 0.05). After adding another four MR models and performing sensitivity analyses, we found a 1-SD increase in the xenobiotics 4-vinylphenol sulfate was associated with ~22% higher risk of HF (OR [95%CI], 1.22 [1.07–1.38]).Conclusions: We revealed that the 4-vinylphenol sulfate may nominally increase the risk of HF by 22% after using a two-sample MR approach. Our findings may provide novel insights into the pathogenesis underlying HF and novel strategies for HF prevention.

scholarly journals The use of two-sample methods for Mendelian randomization analyses on single large datasets

2020 ◽  
Author(s):  
Cosetta Minelli ◽  
M. Fabiola Del Greco ◽  
Diana A. van der Plaat ◽  
Jack Bowden ◽  
Nuala A. Sheehan ◽  
...  
Keyword(s):  
Mendelian Randomization ◽  
Causal Effect ◽  
Meta Analysis ◽  
Effect Estimate ◽  
List Type ◽  
Causal Relationships ◽  
Uk Biobank ◽  
Current Availability ◽  
Association Data ◽  
Very High

AbstractBackgroundWith genome-wide association data for many exposures and outcomes now available from large biobanks, one-sample Mendelian randomization (MR) is increasingly used to investigate causal relationships. Many robust MR methods are available to address pleiotropy, but these assume independence between the gene-exposure and gene-outcome association estimates. Unlike in two-sample MR, in one-sample MR the two estimates are obtained from the same individuals, and the assumption of independence does not hold in the presence of confounding.MethodsWith simulations mimicking a typical study in UK Biobank we assessed the performance, in terms of bias and precision of the MR estimate, of the fixed-effect and (multiplicative) random-effects meta-analysis method, weighted median estimator, weighted mode estimator and MR-Egger regression, used in both one-sample and two-sample data. We considered scenarios differing for: presence/absence of a true causal effect; amount of confounding; presence and type of pleiotropy (none, balanced or directional).ResultsEven in the presence of substantial correlation due to confounding, all methods performed well when used in one-sample MR except for MR-Egger, which resulted in bias reflecting direction and magnitude of the confounding. Such bias was much reduced in the presence of very high variability in instrumental strength across variants (I2GX of 97%).ConclusionsTwo-sample MR methods can be safely used for one-sample MR performed within large biobanks, expect for MR-Egger. MR-Egger is not recommended for one-sample MR unless the correlation between the gene-exposure and gene-outcome estimates due to confounding can be kept low, or the variability in instrumental strength is very high.Key MessagesCurrent availability of phenotypic and genetic data from large biobanks, such as UK Biobank, has led to increasing use of one-sample Mendelian randomization (MR) to investigate causal relationships in epidemiological researchRobust MR methods have been developed to address pleiotropy, but they assume independence between the gene-exposure and gene-outcome association estimates; this holds in two-sample MR but not in one-sample MRWe illustrate the practical implications, in terms of bias and precision of the MR causal effect estimate, of using robust two-sample methods in one-sample MR studies performed within large biobanksTwo-sample MR methods can be safely used for one-sample MR performed within large biobanks, expect for MR-Egger regressionMR-Egger is not recommended for one-sample MR unless the correlation between the gene-exposure and gene-outcome estimates due to confounding can be kept low, or the variability in instrumental strength is very high

scholarly journals Decreased choroidal and scleral thicknesses in highly myopic eyes with posterior staphyloma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Un Chul Park ◽  
Eun Kyoung Lee ◽  
Bo Hee Kim ◽  
Baek-Lok Oh
Keyword(s):  
Choroidal Thickness ◽  
Structural Changes ◽  
Meta Analysis ◽  
Cross Sectional Study ◽  
Pathologic Myopia ◽  
Sectional Study ◽  
Cross Sectional ◽  
Swept Source ◽  
Posterior Staphyloma ◽  
Myopic Maculopathy

AbstractIn this cross-sectional study, we investigated choroidal thickness (CT) and scleral thickness (ST) in highly myopic eyes and their associations with ocular factors. Patients underwent widefield swept-source optical coherence tomography (OCT) to measure the CT and ST at the subfovea and 3000 μm superior, inferior, temporal, and nasal to the fovea and macular curvature. A total of 237 eyes (154 patients) were included. At all five measurement points, thinner CTs and STs were associated with longer axial lengths (r = − 0.548 to − 0.357, all P < 0.001) and greater macular curvatures (r = − 0.542 to − 0.305, all P < 0.001). The CT and ST were significantly thinner in eyes with posterior staphyloma than in those without at all measurement points (all P ≤ 0.006) but did not differ between eyes with the wide macular and narrow macular type of staphyloma. Eyes with myopic maculopathy of category ≥ 3 according to the International Meta-Analysis for Pathologic Myopia classification had significantly thinner CTs and STs than those with category ≤ 2 (all P ≤ 0.005). In highly myopic eyes, a decrease in the CT and ST was more pronounced in eyes with more structural changes, such as longer axial length, steeper macular curvature, and the presence of posterior staphyloma.

scholarly journals Healthy adult vegetarians have better renal function than matched omnivores: a cross-sectional study in China

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Kaijie Xu ◽  
Xueying Cui ◽  
Bian Wang ◽  
Qingya Tang ◽  
Jianfang Cai ◽  
...  
Keyword(s):  
Renal Function ◽  
Healthy Adult ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional

The association between meat consumption and the metabolic syndrome: a cross-sectional study and meta-analysis

2021 ◽  
pp. 1-15
Author(s):  
Khemayanto Hidayat ◽  
Wan-Zhan Zhu ◽  
Si-Min Peng ◽  
Jin-Jin Ren ◽  
Meng-Lan Lu ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Fish Consumption ◽  
Meta Analysis ◽  
Meat Consumption ◽  
Cross Sectional Study ◽  
Red Meat ◽  
Inverse Association ◽  
Sectional Study ◽  
Cross Sectional ◽  
The Metabolic Syndrome

Abstract The findings regarding the associations between red meat, fish and poultry consumption, and the metabolic syndrome (Mets) have been inconclusive, and evidence from Chinese populations is scarce. A cross-sectional study was performed to investigate the associations between red meat, fish and poultry consumption, and the prevalence of the Mets and its components among the residents of Suzhou Industrial Park, Suzhou, China. A total of 4424 participants were eligible for the analysis. A logistic regression model was used to estimate the OR and 95 % CI for the prevalence of the Mets and its components according to red meat, fish and poultry consumption. In addition, the data of our cross-sectional study were meta-analysed under a random effects model along with those of published observational studies to generate the summary relative risks (RR) of the associations between the highest v. lowest categories of red meat, fish and poultry consumption and the Mets and its components. In the cross-sectional study, the multivariable-adjusted OR for the highest v. lowest quartiles of consumption was 1·23 (95 % CI 1·02, 1·48) for red meat, 0·83 (95 % CI 0·72, 0·97) for fish and 0·93 (95 % CI 0·74, 1·18) for poultry. In the meta-analysis, the pooled RR for the highest v. lowest categories of consumption was 1·20 (95 % CI 1·06, 1·35) for red meat, 0·88 (95 % CI 0·81, 0·96) for fish and 0·97 (95 % CI 0·85, 1·10) for poultry. The findings of both cross-sectional studies and meta-analyses indicated that the association between fish consumption and the Mets may be partly driven by the inverse association of fish consumption with elevated TAG and reduced HDL-cholesterol and, to a lesser extent, fasting plasma glucose. No clear pattern of associations was observed between red meat or poultry consumption and the components of the Mets. The current findings add weight to the evidence that the Mets may be positively associated with red meat consumption, inversely associated with fish consumption and neutrally associated with poultry consumption.

scholarly journals Cervical cancer: Renal complications and survival after percutaneous nephrostomy

2016 ◽  
Vol 62 (3) ◽  
pp. 255-261 ◽  
Author(s):  
Alzira Carvalho Paula de Souza ◽  
Alfredo Nunes Souza ◽  
Rubens Kirsztajn ◽  
Gianna Mastroianni Kirsztajn
Keyword(s):  
Blood Pressure ◽  
Cervical Cancer ◽  
Renal Function ◽  
Percutaneous Nephrostomy ◽  
Cross Sectional Study ◽  
Obstructive Nephropathy ◽  
Cross Sectional ◽  
Low Blood Pressure ◽  
Northern Brazil

SUMMARY Introduction: Obstructive nephropathy is a frequent complication in the course of advanced cervical cancer (CC), and ultrasonography-guided percutaneous nephrostomy (PCN) is a well established technique for fast ureteral desobstruction. Objective: To identify possible factors related to the survival and quality of life of patients with advanced CC presenting acute urinary obstructive complications that after desobstruction by PCN recovered urinary flux and renal function. Method: This is an analytical, descriptive, cross-sectional study that included 45 patients with CC who underwent PCN and were divided into 2 groups: “death” (DG) and “survival” (SG), in a public hospital that is reference for oncologic diseases in Northern Brazil. Results: The mean serum creatinine of the patients preceding PCN was >10 mg/dL, and after PCN <2 mg/dL. The cutoffs of 8.7 g/dL for Hb (p=0.0241) and 27% for Ht (p=0.0065) indicated the values that better discriminate the outcomes of the groups. The presence of low blood pressure was statistically correlated (p=0.0037) to the outcome “death”. Changes in glomerular filtration rate (already reduced in all cases) were not associated to the levels of Hb/Ht or to the outcome “death” during the nephrological follow-up. Conclusion: PCN was responsible for the recovery of renal function in 61.7% of the patients, leading to interruption of renal replacement therapy (RRT) in all of those patients. Hb levels >8.7g/dL and Ht >27% were associated to longer survival, and the presence of low blood pressure during follow-up was associated with progression to death.

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