Causal associations of obesity with chronic kidney disease and arterial stiffness: a Mendelian randomization study

2021 ◽  
Author(s):  
Chaojie Ye ◽  
Lijie Kong ◽  
Zhiyun Zhao ◽  
Mian Li ◽  
Shuangyuan Wang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Standard Deviation ◽  
Kidney Disease ◽  
Single Nucleotide Polymorphisms ◽  
Arterial Stiffness ◽  
Genetic Risk ◽  
Mendelian Randomization ◽  
Genetic Risk Score ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

Abstract Purpose Observational studies have associated obesity with chronic kidney disease (CKD) and arterial stiffness, but the causality remains unclear. We aimed to investigate the causality of obesity with CKD and arterial stiffness using Mendelian randomization (MR) analysis. Methods We genotyped 14 body mass index (BMI)-associated variants validated in East Asians in 11384 Chinese adults. A genetic risk score based on the 14 variants and the 14 individual single nucleotide polymorphisms were respectively used as instrumental variables (IVs). CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m 2. Arterial stiffness was defined as brachial-ankle pulse wave velocity >1550 cm/s. Results Using the genetic risk score as the IV, we demonstrated causal relations of each 1-standard deviation increment in BMI with CKD (odds ratio [OR]: 2.36; 95% confidence interval [CI]: 1.11-5.00) and arterial stiffness (OR: 1.71; 95% CI: 1.22-2.39). Using the 14 single nucleotide polymorphisms individually as IVs, each 1-standard deviation increment in BMI casually associated with CKD (OR: 2.58; 95% CI: 1.39-4.79) and arterial stiffness (OR: 1.87; 95% CI: 1.24-2.81) in the inverse-variance weighted analysis, and MR-Egger regression revealed no evidence of horizontal pleiotropy (Both P for intercept≥0.34). The causality between obesity and CKD was validated in two-sample MR analysis among Europeans (681275 of Genetic Investigation of ANthropometric Traits and 133413 of CKD Genetics). Conclusions This study provided novel insights into causality of obesity with CKD and arterial stiffness, highlighting the importance of weight management for primary prevention and control of subclinical vascular diseases.

Will patient’s genetic profile help to choose treatment method of atrial fibrillation?

2019 ◽  
Vol 3 (52) ◽  
pp. 29-30
Author(s):  
Artur Fuglewicz
Keyword(s):  
Atrial Fibrillation ◽  
Single Nucleotide Polymorphisms ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Treatment Method ◽  
Genetic Profile ◽  
Nucleotide Polymorphisms ◽  
Genetic Score ◽  
Single Nucleotide

The paper comments an attempt of genetic score creation of potential atrial fibrillation ablation failure or recurrence AF. This genetic risk score is based on single nucleotide polymorphisms (SNPs) analysis.

scholarly journals Causal Effect of Adiposity Measures on Blood Pressure Traits in 2 Urban Swedish Cohorts: A Mendelian Randomization Study

2021 ◽  
Author(s):  
Alice Giontella ◽  
Luca A. Lotta ◽  
John D. Overton ◽  
Aris Baras ◽  
Pietro Minuz ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Genetic Risk ◽  
Mendelian Randomization ◽  
Genetic Risk Score ◽  
Risk Scores ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Waist To Hip Ratio ◽  
Diet And Cancer

Background Different adiposity traits may be causally related to hypertension in different ways. By using genetic variants as randomly allocated proxies for studying the effect of modifying adiposity traits, the Mendelian randomization approach can be used to investigate this. Methods and Results In this study, we used 4 different genetic risk scores (GRS; GRS‐BMI 565 , GRS‐WHR 324 , GRS‐VAT 208 , GRS‐BF 81 ) including hundreds of single nucleotide polymorphisms associated with body mass index, waist‐to‐hip ratio, visceral adipose tissue, and body fat, respectively. These were applied as instrumental variables in Mendelian randomization analyses. Two Swedish urban‐based cohort studies, the Malmö Diet and Cancer, and the Malmö Preventive 795Projects were used to obtain genetic association estimates with blood pressure (BP). In both the Malmö Preventive Projects and Malmö Diet and Cancer studies, except for that for body fat, all of the genetic risk scores were significantly associated with systolic BP and diastolic BP, but with different magnitudes. In particular, in both cohorts, each standard deviation increase in the genetic risk score made up by the 324 single nucleotide polymorphisms associated with waist‐to‐hip ratio was associated with doubling of the likelihood of hypertension prevalence at baseline. However, only the genetic risk score made up by the 565 SNPs associated with body mass index was significantly associated with hypertension incidence during 23.6±4.3 years of follow‐up in the Malmö Preventive Project. Conclusions We support a causal link between genetically mediated adiposity, especially waist‐to‐hip ratio and body mass index, and BP traits including hypertension prevalence and, for the first time to our knowledge, hypertension incidence. The differences in magnitude between these associations might suggest different mechanisms by which different adiposity affects BP/hypertension and consequently may indicate that tailored interventions are needed to reduce cardiovascular risk.

scholarly journals Inference of a causal relation between low-density lipoprotein cholesterol and hypertension using mendelian randomization analysis

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Tae-Hwa Go ◽  
Kyeong Im Kwak ◽  
Ji-Yun Jang ◽  
Minheui Yu ◽  
Hye Sim Kim ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Observational Study ◽  
Genetic Risk ◽  
Mendelian Randomization ◽  
Risk Scores ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genetic Risk Scores ◽  
The Relationship ◽  
Randomization Analysis

Abstract Background It is known in some studies that higher the LDL-C, the greater the risk of developing cardiovascular disease. However, studies of the causal effects between LDL-C and hypertension are limited by their observational study design, and genetic epidemiology studies of associations between LDL-C and hypertension are lacking, as are studies using data for Koreans. In this study, we confirmed the causal effect of LDL-C on hypertension using Korean chip data. Method The epidemiology and genotype data were collected from the Korean Genome and Epidemiology Study conducted by the Korea National Institute of Health and covered 20,701 subjects. Single-nucleotide polymorphisms associated with LDL-C were selected (p-value < 5 × 10− 8) from the Global Lipids Genetics Consortium database, and Mendelian randomization analysis (MRA) was performed with counted genetic risk scores and weighted genetic risk scores (WGRSs) for 24 single-nucleotide polymorphisms. Result The assumptions for MRA were statistically confirmed, and WGRSs showed a strong association with LDL-C. Interestingly, while the relationship between LDL-C and hypertension was not statistically significant in the observational study, MRA study demonstrated that the risk of hypertension increased as LDL-C increased in both men and women. Conclusions The results of this study confirmed that the relationship between LDL-C and hypertension is greatly influenced by genetic information.

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