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.

scholarly journals Missing single nucleotide polymorphisms in Genetic Risk Scores: A simulation study

PLoS ONE ◽  
2018 ◽  
Vol 13 (7) ◽  
pp. e0200630 ◽  
Author(s):  
Miguel Chagnon ◽  
Jennifer O’Loughlin ◽  
James C. Engert ◽  
Igor Karp ◽  
Marie-Pierre Sylvestre
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Simulation Study ◽  
Genetic Risk ◽  
Risk Scores ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genetic Risk Scores

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 &lt;60 mL/min/1.73 m 2. Arterial stiffness was defined as brachial-ankle pulse wave velocity &gt;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.

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.

Abstract P163: Are Coronary Artery Disease and Type 2 Diabetes Causally Related to Age of Menopause?

Circulation ◽  
2016 ◽  
Vol 133 (suppl_1) ◽  
Author(s):  
N. Charlotte Onland-Moret ◽  
Claire Lovern ◽  
Marlies Voorhuis ◽  
Ching-Ti Liu ◽  
Frank J Broekmans ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Genetic Risk ◽  
Risk Scores ◽  
Nucleotide Polymorphisms ◽  
Natural Menopause ◽  
Single Nucleotide ◽  
Genotyping Array ◽  
Genetic Risk Scores ◽  
Increased Risk

Background: Women who enter the menopause at a younger age, are at an increased risk of cardiovascular disease (CVD) and type 2 diabetes (T2D) in later life. However, we have previously reported that development of an unfavourable cardiovascular risk profile premenopausally accelerates the onset of menopause. Furthermore, we reported that women who were diagnosed with diabetes at a very young age also reached menopause earlier. Hence, the direction of the relationship between coronary heart disease (CHD), T2D and the onset of menopause is unclear, and whether the associations are causal is also unclear. Hypothesis: In this study we hypothesize that CHD and/or T2D are causally related to the age of menopause, and studied this using genetic risk scores for CHD and T2D. Methods: Single nucleotide polymorphisms which had previously reached genome-wide significance for CHD and T2D were, individually and as a genetic risk score, tested for an association with age at natural menopause in over 50,000 women from three large consortia: the ITMAT/Broad/CARe (IBC) consortium, the ReproGen consortium, and the EPIC-InterAct consortium. From these consortia all women with a known age at natural menopause between 40 and 60 years were included. We used the genotyping array of the IBC consortium for the selection of the SNPs. The IBC array is a gene-centric genotyping array developed for replication and fine mapping and incorporates about 50K SNPs that capture information on 2000 genetic regions related to cardiovascular, inflammatory, and metabolic regions. The selected SNPs were also requested for analyses in the other two consortia. A total of 18 single nucleotide polymorphisms for CHD and 28 for T2D were selected. In the EPIC-InterAct study we used these SNPs to calculate unweighted individual level genetic risk scores. Results: No statistically significant associations were found for any of the CHD SNPs, nor for the T2D SNPs, nor for the genetic risk scores. Conclusions: Previous findings that women with an increased risk of CHD or T2D also have an increased risk of entering the menopause at younger ages, could not be supported by our data. Furthermore, the association between cardiometabolic disease and earlier timing of menopause does not seem to be causal. However, this finding does not exclude the possibility that the reverse association can be causal.

scholarly journals Assessing the Causality Factors in the Association between (Abdominal) Obesity and Physical Activity among the Newfoundland Population–-A Mendelian Randomization Analysis

2016 ◽  
Vol 8 ◽  
pp. GEG.S38289 ◽  
Author(s):  
Frank Barning ◽  
Taraneh Abarin
Keyword(s):  
Physical Activity ◽  
Newfoundland And Labrador ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Intervention Strategies ◽  
Nucleotide Polymorphisms ◽  
Fto Gene ◽  
Single Nucleotide ◽  
Similar Association ◽  
Randomization Analysis

A total of 1,263 adults from Newfoundland and Labrador were studied in the research. Body mass index (BMI) and percent trunk fat (PTF) were analyzed as biomarkers for obesity. The Mendelian randomization (MR) approach with two single-nucleotide polymorphisms in the fat-mass and obesity (FTO) gene as instruments was employed to assess the causal effect. In both genders, increasing physical activity significantly reduced BMI and PTF when adjusted for age and the FTO gene. The effect of physical activity was stronger on PTF than BMI. Direct observational analyses showed significant increase in BMI/PTF when physical activity decreased. A similar association in MR analyses was not significant. The association between physical activity and BMI/PTF could be due to reversed causality or common confounding factors. Our study provides insights into the causal contributions of obesity to physical activity in adults. Health intervention strategies to increase physical activity among adults should include some other plans such as improving diet for reducing obesity.

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