scholarly journals Cardiometabolic risks of SARS-CoV-2 hospitalization using Mendelian Randomization

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Noah Lorincz-Comi ◽  
Xiaofeng Zhu
Keyword(s):  
Pulse Pressure ◽  
Type Ii Diabetes ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Risk Estimation ◽  
Estimation Method ◽  
Large Sample Size ◽  
Sample Type ◽  
Type Ii ◽  
Causal Inferences

AbstractMany cardiometabolic conditions have demonstrated associative evidence with COVID-19 hospitalization risk. However, the observational designs of the studies in which these associations are observed preclude causal inferences of hospitalization risk. Mendelian Randomization (MR) is an alternative risk estimation method more robust to these limitations that allows for causal inferences. We applied four MR methods (MRMix, IMRP, IVW, MREgger) to publicly available GWAS summary statistics from European (COVID-19 GWAS n = 2956) and multi-ethnic populations (COVID-19 GWAS n = 10,908) to better understand extant causal associations between Type II Diabetes (GWAS n = 659,316), BMI (n = 681,275), diastolic and systolic blood pressure, and pulse pressure (n = 757,601 for each) and COVID-19 hospitalization risk across populations. Although no significant causal effect evidence was observed, our data suggested a trend of increasing hospitalization risk for Type II diabetes (IMRP OR, 95% CI 1.67, 0.96–2.92) and pulse pressure (OR, 95% CI 1.27, 0.97–1.66) in the multi-ethnic sample. Type II diabetes and Pulse pressure demonstrates a potential causal association with COVID-19 hospitalization risk, the proper treatment of which may work to reduce the risk of a severe COVID-19 illness requiring hospitalization. However, GWAS of COVID-19 with large sample size is warranted to confirm the causality.

scholarly journals Cardiometabolic risks of SARS-CoV-2 hospitalization using Mendelian Randomization

2021 ◽  
Author(s):  
Noah J Lorincz-Comi ◽  
Xiaofeng Zhu
Keyword(s):  
Pulse Pressure ◽  
Type Ii Diabetes ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Risk Estimation ◽  
Estimation Method ◽  
Large Sample Size ◽  
Sample Type ◽  
Type Ii ◽  
Causal Inferences

Many cardiometabolic conditions have demonstrated associative evidence with COVID-19 hospitalization risk. However, the observational designs of the studies in which these associations are observed preclude causal inferences of hospitalization risk. Mendelian Randomization (MR) is an alternative risk estimation method more robust to these limitations that allows for causal inferences. We applied four MR methods (MRMix, IMRP, IVW, MREgger) to publicly available GWAS summary statistics from European (COVID-19 GWAS n=2,956) and multi-ethnic populations (COVID-19 GWAS n=10,808) to better understand extant causal associations between Type II Diabetes (GWAS n=659,316), BMI (n=681,275), diastolic and systolic blood pressure, and pulse pressure (n=757,601 for each) and COVID-19 hospitalization risk across populations. Although no significant causal effect evidence was observed, our data suggested a trend of increasing hospitalization risk for Type II diabetes (IMRP OR, 95% CI: 1.67, 0.96-2.92) and pulse pressure (OR, 95% CI: 1.27, 0.97-1.66) in the multi-ethnic sample. Type II diabetes and Pulse pressure demonstrates a potential causal association with COVID-19 hospitalization risk, the proper treatment of which may work to reduce the risk of a severe COVID-19 illness requiring hospitalization. However, GWAS of COVID-19 with large sample size is warranted to confirm the causality.

scholarly journals Cardiometabolic Risks of SARS-CoV-2 Hospitalization Using Mendelian Randomization

2020 ◽  
Author(s):  
Noah Lorincz-Comi ◽  
Xiaofeng Zhu
Keyword(s):  
Pulse Pressure ◽  
Type Ii Diabetes ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Risk Estimation ◽  
Estimation Method ◽  
Large Sample Size ◽  
Type Ii ◽  
Causal Inferences ◽  
Ethnic Populations

Abstract IntroMany cardiometabolic conditions have demonstrated associative evidence with COVID-19 hospitalization risk. However, the observational designs of the studies in which these associations are observed preclude causal inferences of hospitalization risk. Mendelian Randomization (MR) is an alternative risk estimation method more robust to these limitations that allows for causal inferences.Methods & materialsWe applied four MR methods (MRMix, IMRP, IVW, MREgger) to publicly available GWAS summary statistics from European (COVID-19 GWAS n=2,956) and multi-ethnic populations (COVID-19 GWAS n=10,808) to better understand extant causal associations between Type II Diabetes (GWAS n=659,316), BMI (n=681,275), diastolic and systolic blood pressure, and pulse pressure (n=757,601 for each) and COVID-19 hospitalization risk across populations. ResultsAlthough no significant causal effect evidence was observed, our data suggested a trend of increasing hospitalization risk for Type II diabetes (IMRP OR, 95% CI: 1.67, 0.96-2.92) and pulse pressure (OR, 95% CI: 1.27, 0.97-1.66) in the multi-ethnic sample. ConclusionsType II diabetes and Pulse pressure demonstrates a potential causal association with COVID-19 hospitalization risk, the proper treatment of which may work to reduce the risk of a severe COVID-19 illness requiring hospitalization. However, GWAS of COVID-19 with large sample size is warranted to confirm the causality.

Determinants of brachial artery mean 24 h pulse pressure in individuals with Type II diabetes mellitus and untreated mild hypertension

2002 ◽  
Vol 102 (2) ◽  
pp. 177 ◽  
Author(s):  
Robert A. J. M. van DIJK ◽  
Frans J. van ITTERSUM ◽  
Nico WESTERHOF ◽  
Els M. van DONGEN ◽  
Otto KAMP ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Brachial Artery ◽  
Pulse Pressure ◽  
Type Ii Diabetes ◽  
Mild Hypertension ◽  
Type Ii Diabetes Mellitus ◽  
Type Ii

scholarly journals The Potential Effect of Aberrant Testosterone Levels on Common Diseases: A Mendelian Randomization Study

Genes ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 721
Author(s):  
Ali Alamdar Shah Syed ◽  
Lin He ◽  
Yongyong Shi
Keyword(s):  
Type Ii Diabetes ◽  
Mendelian Randomization ◽  
Serum Testosterone ◽  
Potential Effect ◽  
Type Ii ◽  
Degenerative Diseases ◽  
Testosterone Levels ◽  
Unit Increase ◽  
Low Levels ◽  
Genetic Instruments

Testosterone has historically been linked to sexual dysfunction; however, it has recently been shown to affect other physical and mental attributes. We attempted to determine whether changes in serum testosterone could play a role in chronic or degenerative diseases. We used two separate genetic instruments comprising of variants from JMJD1C and SHBG regions and conducted a two-sample Mendelian randomization for type II diabetes (T2D), gout, rheumatoid arthritis (RA), schizophrenia, bipolar disorder, Alzheimer’s disease and depression. For the JMJD1C locus, one unit increase in log transformed testosterone was significantly associated with RA (OR = 1.69, p = 0.02), gout (OR = 0.469, p = 0.001) and T2D (OR = 0.769, p = 0.048). Similarly, one unit increase in log transformed testosterone using variants from the SHBG locus was associated with depression (OR = 1.02, p = 0.001), RA (OR = 1.32, p < 0.001) and T2D (OR = 0.88, p = 0.003). Our results show that low levels of serum testosterone levels may cause gout and T2D, while higher than normal levels of testosterone may result in RA and depression. Our findings suggest that fluctuations in testosterone levels may have severe consequences that warrant further investigation.

Determinants of brachial artery mean 24 h pulse pressure in individuals with Type II diabetes mellitus and untreated mild hypertension

2002 ◽  
Vol 102 (2) ◽  
pp. 177-186 ◽  
Author(s):  
Robert A.J.M. VAN DIJK ◽  
Frans J. VAN ITTERSUM ◽  
Nico WESTERHOF ◽  
Els M. VAN DONGEN ◽  
Otto KAMP ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Brachial Artery ◽  
Pulse Pressure ◽  
Type Ii Diabetes ◽  
Mild Hypertension ◽  
Fasting Glucose ◽  
Augmentation Index ◽  
Arterial Compliance ◽  
Diabetes Duration ◽  
Type Ii

Brachial artery pulse pressure is a predictor of (cardiovascular) morbidity, but its determinants in individuals with Type II diabetes and untreated mild hypertension have not been elucidated. We therefore cross-sectionally investigated determinants of brachial artery mean 24h pulse pressure in 60 individuals (40 males; age, mean±S.D., 57.8±7.5 years) with Type II diabetes [median diabetes duration (interquartile range), 6.3 (3.6-10.1) years] and untreated mild hypertension [sitting blood pressure >140/90mmHg and <190/120mmHg (mean of two consecutive auscultatory office measurements after 5min of rest)]. We measured (1) three potential determinants reflecting different aspects of central artery stiffness [the overall systemic arterial compliance, the aortic augmentation index and 1/(regional carotido-femoral transit time)], (2) structural and functional changes of the circulatory system often observed in Type II diabetes, and (3) diabetes-associated metabolic variables. After adjustment for age, gender and mean arterial pressure, brachial artery pulse pressure was associated with autonomic function [standardized regression coefficient (β), -0.27 (P = 0.01)], blood pressure decline during sleep [standardized β, -0.32 (P = 0.002)], fasting glucose concentration [standardized β, 0.26 (P = 0.01)], HbA1c concentration [standardized β, 0.27 (P = 0.003)] and diabetes duration [standardized β, 0.28 (P = 0.002)] in linear regression analyses. In a combined multivariate model, brachial artery pulse pressure was independently determined by gender [1 = male, 2 = female; standardized β, 0.24 (P = 0.01)], diabetes duration [standardized β, 0.18 (P = 0.03)], mean arterial pressure [standardized β, 0.32 (P = 0.002)], systemic arterial compliance [standardized β, -0.23 (P = 0.02)] and fasting glucose concentration [standardized β, 0.20 (P = 0.02)]. Aortic augmentation index and 1/(carotido-femoral transit time) were not independently associated with pulse pressure. In conclusion, in individuals with Type II diabetes and untreated mild hypertension, brachial artery pulse pressure is determined mainly by proximal aortic stiffness in a way which is not strongly influenced by peripheral pulse wave reflection. Approx. 60% of the variance in brachial artery pulse pressure could be explained by potentially modifiable determinants.

scholarly journals Impact of Liability to Periodontitis on Glycemic Control and Type II Diabetes Risk: A Mendelian Randomization Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Parth D. Shah ◽  
C. M. Schooling ◽  
Luisa N. Borrell
Keyword(s):  
Type Ii Diabetes ◽  
Mendelian Randomization ◽  
Fasting Glucose ◽  
Association Studies ◽  
Sensitivity Analyses ◽  
Genome Wide Association Studies ◽  
Type Ii ◽  
Nucleotide Polymorphisms ◽  
Causal Association ◽  
East Asians

While the association of periodontitis with Type II diabetes (T2DM) is well-established, the causal relationship remains uncertain. We examined the causal association of periodontitis with glycemic traits (HbA1c, fasting glucose, and fasting insulin) and T2DM using Mendelian randomization (MR) taking advantage of large genome-wide association studies of European and East Asian adults, i.e., the UK Biobank (n ≈ 350,000) (HbA1c), trans-ancestral MAGIC (HbA1c, fasting glucose, and insulin), and DIAMANTE (74,124 cases/824,006 controls), and AGEN for T2DM in Europeans and East Asians, respectively. Periodontitis was instrumented using single-nucleotide polymorphisms (SNPs), strongly and independently predicting liability to periodontitis in each ancestry group. SNP-specific Wald estimates were combined using inverse variance weighting. Sensitivity analyses were performed using the weighted median and MR-Egger with meta-analysis of MR estimates for Europeans and East Asians. Genetically instrumented liability to periodontitis was not associated with glycemic traits or T2DM in either ancestry or when ancestry specific estimates were meta-analyzed. Our findings do not support a causal association of liability to periodontitis with glycemic traits or T2DM. However, further research is required confirming these findings among other racial/ethnic groups, especially groups who carry a heavy burden of both periodontitis and T2DM.

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