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 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 Correlation between C-reactive protein levels with leading risk factors for cardiovascular disease in men

2008 ◽  
Vol 61 (3-4) ◽  
pp. 164-168 ◽  
Author(s):  
Bosa Mirjanic-Azaric ◽  
Mirjana Djeric ◽  
Maja Vrhovac ◽  
Ljiljana Males-Bilic
Keyword(s):  
Blood Pressure ◽  
Body Mass Index ◽  
Total Cholesterol ◽  
Body Mass ◽  
Ldl Cholesterol ◽  
Hdl Cholesterol ◽  
C Reactive Protein ◽  
Protein Levels ◽  
Reactive Protein ◽  
Significant Difference

Introduction The aim of this study was to estimate the correlation between C-reactive protein levels and leading risk factors for cardiovascular disease in men. Material and methods The study included 183 working capable men chosen randomly from the regular systematical check-up in Health Centre Banja Luka in 2006. Standard laboratory methods were used to establish the following: total cholesterol, triglyceride and HDL-cholesterol level and LDL-cholesterol level was calculated. . High sensitive C-reactive protein level was measured by immunuturbidimetric method CRP (Latex) HS Roche Diagnostic. Results Average values of high sensitive C-reactive protein for the whole group was 1.69 mg/L, total cholesterol 5.73 mmol/L, HDL-cholesterol 1.38 mmol/L, LDL-cholesterol 3.40 mmol/L. The average value for the systolic blood pressure was 132.9 mmHg, dyastolic blood pressure 85.4 mmHg, and body mass index 28.47 kg/m2. Out of the overall number of examinees, 74 were smokers (40.4%) and 109 (59.6%) nonsmokers. The statistical analysis showed that there was a statistically significant difference between C-reactive protein level in the group with dyastolic blood pressure below 90 mmHg and above (p<0.05); as well as statistically significant difference between the group with desirable body mass index and the group with increased BMI(p<0.05). Discussion The results of our study show that there is a significant correlation between CRP levels and high blood pressure, and in persons with increased body mass index. However, there was no correlation between CRP levels and total cholesterol HDL and LDL cholesterol levels. Conclusion High sensitive CRP screening is useful in early detection and prevention of cardiovascular diseases.

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 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.

Body Mass Index, but Not Physical Activity, Is Associated with C-Reactive Protein

2003 ◽  
Vol 35 (7) ◽  
pp. 1160-1166 ◽  
Author(s):  
ERIC S. RAWSON ◽  
PATTY S. FREEDSON ◽  
STAVROULA K. OSGANIAN ◽  
CHARLES E. MATTHEWS ◽  
GEORGE REED ◽  
...  
Keyword(s):  
Physical Activity ◽  
Body Mass Index ◽  
Body Mass ◽  
C Reactive Protein ◽  
Reactive Protein

Serum C reactive protein levels and genetic variation in the CRP gene are not associated with the prevalence, incidence or progression of osteoarthritis independent of body mass index

2010 ◽  
Vol 69 (11) ◽  
pp. 1976-1982 ◽  
Author(s):  
Hanneke J M Kerkhof ◽  
Sita M A Bierma-Zeinstra ◽  
Martha C Castano-Betancourt ◽  
Moniek P de Maat ◽  
Albert Hofman ◽  
...  
Keyword(s):  
Systematic Review ◽  
Body Mass Index ◽  
Genetic Variation ◽  
Body Mass ◽  
Analysis Of Covariance ◽  
C Reactive Protein ◽  
Knee Oa ◽  
Reactive Protein ◽  
Serum Crp ◽  
The Relationship

ObjectiveTo study the relationship between serum C reactive protein (CRP) levels, genetic variation in the CRP gene and the prevalence, incidence and progression of radiographic osteoarthritis (ROA) in the Rotterdam Study-I (RS-I). A systematic review of studies assessing the relationship between osteoarthritis (OA) and CRP levels was also performed.MethodsThe association between CRP levels and genetic variation in the CRP gene and ROA was examined in 861 patients with hand OA, 718 with knee OA, 349 with hip OA and 2806 controls in the RS-I using one-way analysis of covariance and logistic regression, respectively. PubMed was searched for articles published between January 1992 and August 2009 assessing the relationship between CRP levels and OA.ResultsIn RS-I the prevalence of knee OA, but not hip OA or hand OA, was associated with 14% higher serum CRP levels compared with controls (p=0.001). This association disappeared after adjustment for age and especially body mass index (BMI) (p=0.33). Genetic variation of the CRP gene was not consistently associated with the prevalence, incidence or progression of OA within RS-I. The systematic review included 18 studies (including RS-I) on serum CRP levels and the prevalence, incidence or progression of OA. Consistently higher crude CRP levels were found in cases of prevalent knee OA compared with controls. No association was observed between serum CRP levels and the prevalence of knee OA following adjustment for BMI (n=3 studies, meta-analysis p value=0.61).ConclusionThere is no evidence of association between serum CRP levels or genetic variation in the CRP gene with the prevalence, incidence or progression of OA independent of BMI.

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