scholarly journals Gallstones, Body Mass Index, C‐reactive Protein and Gallbladder Cancer – Mendelian Randomization Analysis of Chilean and European Genotype Data

Hepatology ◽  
2020 ◽  
Author(s):  
Carol Barahona Ponce ◽  
Dominique Scherer ◽  
Regina Brinster ◽  
Felix Boekstegers ◽  
Katherine Marcelain ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Gallbladder Cancer ◽  
Body Mass ◽  
Mendelian Randomization ◽  
Genotype Data ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Mendelian Randomization Analysis ◽  
European Genotype ◽  
Randomization Analysis

scholarly journals Leveraging genetic data to elucidate the relationship between Covid-19 and ischemic stroke

2021 ◽  
Author(s):  
Verena Zuber ◽  
Alan Cameron ◽  
Evangelos P. Myserlis ◽  
Leonardo Bottolo ◽  
Israel Fernandez-Cadenas ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Ischemic Stroke ◽  
Body Mass ◽  
Mendelian Randomization ◽  
Genetic Data ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Increased Risk ◽  
The Relationship ◽  
Randomization Analysis

AbstractBackgroundThe relationship between coronavirus disease 2019 (Covid-19) and ischemic stroke is poorly defined. We aimed to leverage genetic data to investigate reported associations.MethodsGenetic association estimates for liability to Covid-19 and cardiovascular traits were obtained from large-scale consortia. Analyses primarily focused on critical Covid-19, defined as hospitalization with Covid-19 requiring respiratory support or resulting in death. Cross-trait linkage disequilibrium score regression was used to estimate genetic correlations of critical Covid-19 with ischemic stroke, other related cardiovascular outcomes, and risk factors common to both Covid-19 and cardiovascular disease (body mass index, smoking and chronic inflammation, estimated using C-reactive protein). Mendelian randomization analysis was performed to investigate whether liability to critical Covid-19 was associated with increased risk of any of the cardiovascular outcomes for which genetic correlation was identified.ResultsThere was evidence of genetic correlation between critical Covid-19 and ischemic stroke (rg=0.29, FDR p-value=4.65×10−3), body mass index (rg=0.21, FDR-p-value=6.26×10−6) and C-reactive protein (rg=0.20, FDR-p-value=1.35×10−4), but none of the other considered traits. In Mendelian randomization analysis, liability to critical Covid-19 was associated with increased risk of ischemic stroke (odds ratio [OR] per logOR increase in genetically predicted critical Covid-19 liability 1.03, 95% confidence interval 1.00-1.06, p-value=0.03). Similar estimates were obtained when considering ischemic stroke subtypes. Consistent estimates were also obtained when performing statistical sensitivity analyses more robust to the inclusion of pleiotropic variants, including multivariable Mendelian randomization analyses adjusting for potential genetic confounding through body mass index, smoking and chronic inflammation. There was no evidence to suggest that genetic liability to ischemic stroke increased the risk of critical Covid-19.ConclusionsThese data support that liability to critical Covid-19 is associated with an increased risk of ischemic stroke. The host response predisposing to severe Covid-19 is likely to increase the risk of ischemic stroke, independent of other potentially mitigating risk factors.

scholarly journals Causal Effects of Body Mass Index on Cardiometabolic Traits and Events: A Mendelian Randomization Analysis

2014 ◽  
Vol 94 (2) ◽  
pp. 312 ◽  
Author(s):  
Michael V. Holmes ◽  
Leslie A. Lange ◽  
Tom Palmer ◽  
Matthew B. Lanktree ◽  
Kari E. North ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Mendelian Randomization ◽  
Causal Effects ◽  
Mendelian Randomization Analysis ◽  
Randomization Analysis ◽  
Cardiometabolic Traits

scholarly journals C-reactive protein levels and body mass index: elucidating direction of causation through reciprocal Mendelian randomization

2010 ◽  
Vol 35 (2) ◽  
pp. 300-308 ◽  
Author(s):  
N J Timpson ◽  
B G Nordestgaard ◽  
R M Harbord ◽  
J Zacho ◽  
T M Frayling ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Mendelian Randomization ◽  
C Reactive Protein ◽  
Protein Levels ◽  
Reactive Protein ◽  
Direction Of Causation

scholarly journals Causal Effects of Body Mass Index on Cardiometabolic Traits and Events: A Mendelian Randomization Analysis

2014 ◽  
Vol 94 (2) ◽  
pp. 198-208 ◽  
Author(s):  
Michael V. Holmes ◽  
Leslie A. Lange ◽  
Tom Palmer ◽  
Matthew B. Lanktree ◽  
Kari E. North ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Mendelian Randomization ◽  
Causal Effects ◽  
Mendelian Randomization Analysis ◽  
Randomization Analysis ◽  
Cardiometabolic Traits

scholarly journals Age-varying genetic associations and implications for bias in Mendelian randomization analyses

2021 ◽  
Author(s):  
Jeremy A Labrecque ◽  
Sonja A Swanson
Keyword(s):  
Body Mass Index ◽  
Alcohol Consumption ◽  
Body Mass ◽  
Genetic Variants ◽  
Ldl Cholesterol ◽  
Mendelian Randomization ◽  
Uk Biobank ◽  
Genetic Associations ◽  
C Reactive Protein ◽  
Reactive Protein

Estimates from conventional Mendelian randomization (MR) analyses can be biased when the genetic variants proposed as instruments vary over age in their relationship with the exposure. For four exposures commonly studied using MR, we assessed the degree to which their relationship with genetic variants commonly used as instruments varies by age using flexible, spline-based models in UK Biobank data. Using these models, we then estimated how biased MR estimates would be due to age-varying relationships using plasmode simulations. We found that most genetic variants had age-varying relationships with the exposure for which they are a proposed instrument. Body mass index and LDL cholesterol had the most variation while alcohol consumption had very little. This variation over age led to small potential biases in some cases (e.g. alcohol consumption and C-reactive protein) and large potential biases for many proposed instruments for BMI and LDL.

scholarly journals Leveraging Genetic Data to Elucidate the Relationship Between COVID‐19 and Ischemic Stroke

2021 ◽  
Author(s):  
Verena Zuber ◽  
Alan Cameron ◽  
Evangelos P. Myserlis ◽  
Leonardo Bottolo ◽  
Israel Fernandez‐Cadenas ◽  
...  
Keyword(s):  
Risk Factors ◽  
Body Mass Index ◽  
Ischemic Stroke ◽  
Body Mass ◽  
Mendelian Randomization ◽  
Genetic Data ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Increased Risk ◽  
The Relationship

Background The relationship between COVID‐19 and ischemic stroke is poorly understood due to potential unmeasured confounding and reverse causation. We aimed to leverage genetic data to triangulate reported associations. Methods and Results Analyses primarily focused on critical COVID‐19, defined as hospitalization with COVID‐19 requiring respiratory support or resulting in death. Cross‐trait linkage disequilibrium score regression was used to estimate genetic correlations of critical COVID‐19 with ischemic stroke, other related cardiovascular outcomes, and risk factors common to both COVID‐19 and cardiovascular disease (body mass index, smoking and chronic inflammation, estimated using C‐reactive protein). Mendelian randomization analysis was performed to investigate whether liability to critical COVID‐19 was associated with increased risk of any cardiovascular outcome for which genetic correlation was identified. There was evidence of genetic correlation between critical COVID‐19 and ischemic stroke (r g =0.29, false discovery rate [FDR]=0.012), body mass index (r g =0.21, FDR=0.00002), and C‐reactive protein (r g =0.20, FDR=0.00035), but no other trait investigated. In Mendelian randomization, liability to critical COVID‐19 was associated with increased risk of ischemic stroke (odds ratio [OR] per logOR increase in genetically predicted critical COVID‐19 liability 1.03, 95% CI 1.00–1.06, P ‐value=0.03). Similar estimates were obtained for ischemic stroke subtypes. Consistent estimates were also obtained when performing statistical sensitivity analyses more robust to the inclusion of pleiotropic variants, including multivariable Mendelian randomization analyses adjusting for potential genetic confounding through body mass index, smoking, and chronic inflammation. There was no evidence to suggest that genetic liability to ischemic stroke increased the risk of critical COVID‐19. Conclusions These data support that liability to critical COVID‐19 is associated with an increased risk of ischemic stroke. The host response predisposing to severe COVID‐19 is likely to increase the risk of ischemic stroke, independent of other potentially mitigating risk factors.

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