scholarly journals Mendelian randomization analysis provides causality of smoking on the expression of ACE2, a putative SARS-CoV-2 receptor

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Hui Liu ◽  
Junyi Xin ◽  
Sheng Cai ◽  
Xia Jiang
Keyword(s):  
Alcohol Consumption ◽  
Research Council ◽  
Mendelian Randomization ◽  
Smoking Initiation ◽  
Smoking Intensity ◽  
Swedish Research Council ◽  
Inverse Variance ◽  
Nominal Significance ◽  
Weighted Median

Background: To understand a causal role of modifiable lifestyle factors in ACE2 expression (a putative SARS-CoV-2 receptor) across 44 human tissues/organs, and in COVID-19 susceptibility and severity, we conducted a phenome-wide two-sample Mendelian randomization (MR) study. Methods: More than 500 genetic variants were used as instrumental variables to predict smoking and alcohol consumption. Inverse-variance weighted approach was adopted as the primary method to estimate a causal association, while MR-Egger regression, weighted median and MR-PRESSO were performed to identify potential horizontal pleiotropy. Results: We found that genetically predicted smoking intensity significantly increased ACE2 expression in thyroid (β=1.468, p=1.8 10-8); and increased ACE2 expression in adipose, brain, colon and liver with nominal significance. Additionally, genetically predicted smoking initiation significantly increased the risk of COVID-19 onset (odds ratio=1.14, p=8.7 10-5). No statistically significant result was observed for alcohol consumption. Conclusions: Our work demonstrates an important role of smoking, measured by both status and intensity, in the susceptibility to COVID-19. Funding: Dr. Jiang is supported by research grants from the Swedish Research Council (VR-2018-02247) and Swedish Research Council for Health, Working Life and Welfare (FORTE-2020-00884).

scholarly journals Adiponectin and human eating behaviour: a Mendelian randomization study

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Awoyemi Abayomi Awofala ◽  
Olusegun Emmanuel Ogundele ◽  
Khalid Olajide Adekoya ◽  
Samuel Adesayo Osundina
Keyword(s):  
Eating Disorders ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Eating Behaviour ◽  
Inverse Variance ◽  
Combining Data ◽  
Modal Regression ◽  
Beta Coefficient ◽  
Weighted Median

Abstract Background Adiponectin plays key roles in regulating appetite and food intake. Altered circulating adiponectin levels have been observed in human eating disorders such as anorexia nervosa, bulimia nervosa or binge eating. In addition, an association between circulating adiponectin levels and human eating behaviour (EB) has been reported. Interestingly, a disturbance in eating behaviour is the defining characteristic of human eating disorders. However, it is unknown whether adiponectin is causally implicated in human EB. We therefore aimed to investigate the causal effect of adiponectin on EB. Results Mendelian randomization (MR) analysis estimated the influence of blood adiponectin on EB by combining data on the association of adiponectin gene (ADIPOQ) variants with adiponectin levels and with three EB factors involving disinhibition, restraint and hunger. Using inverse-variance weighted (IVW) regression method and other complementary MR techniques (weighted median regression, MR Egger and weighted modal regression), the MR analysis revealed a broadly consistent evidence that higher blood adiponectin concentration was significantly associated with increased EB factor disinhibition (beta coefficient for IVW regression [βIVW], 3.05; 95% confidence interval [CI] 1.10, 5.00) but non-significantly associated with increased EB factor restraint (βIVW, 0.17; 95% CI − 1.85, 2.18), and increased EB factor hunger (βIVW, 1.63; 95% CI − 0.75, 4.01). Conclusions Overall, our findings indicate a causal role of adiponectin levels in eating disinhibition but not in eating restraint and hunger.

scholarly journals A Mendelian randomization analysis of the relationship between cardioembolic risk factors and ischemic stroke

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Danyang Tian ◽  
Linjing Zhang ◽  
Zhenhuang Zhuang ◽  
Tao Huang ◽  
Dongsheng Fan
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Mendelian Randomization ◽  
P Wave ◽  
Cardioembolic Stroke ◽  
Large Artery ◽  
Weighted Analysis ◽  
Inverse Variance ◽  
Weighted Median ◽  
Genetically Determined

AbstractObservational studies have shown that several risk factors are associated with cardioembolic stroke. However, whether such associations reflect causality remains unknown. We aimed to determine whether established and provisional cardioembolic risk factors are causally associated with cardioembolic stroke. Genetic instruments for atrial fibrillation (AF), myocardial infarction (MI), electrocardiogram (ECG) indices and N-terminal pro-brain natriuretic peptide (NT-pro BNP) were obtained from large genetic consortiums. Summarized data of ischemic stroke and its subtypes were extracted from the MEGASTROKE consortium. Causal estimates were calculated by applying inverse-variance weighted analysis, weighted median analysis, simple median analysis and Mendelian randomization (MR)-Egger regression. Genetically predicted AF was significantly associated with higher odds of ischemic stroke (odds ratio (OR): 1.20, 95% confidence intervals (CI): 1.16–1.24, P = 6.53 × 10–30) and cardioembolic stroke (OR: 1.95, 95% CI: 1.85–2.06, P = 8.81 × 10–125). Suggestive associations were found between genetically determined resting heart rate and higher odds of ischemic stroke (OR: 1.01, 95% CI: 1.00–1.02, P = 0.005), large-artery atherosclerotic stroke (OR: 1.02, 95% CI: 1.00–1.04, P = 0.026) and cardioembolic stroke (OR: 1.02, 95% CI: 1.00–1.04, P = 0.028). There was no causal association of P‐wave terminal force in the precordial lead V1 (PTFVI), P-wave duration (PWD), NT-pro BNP or PR interval with ischemic stroke or any subtype.

scholarly journals Gallstone disease, diabetes, calcium, triglycerides, smoking and alcohol consumption and pancreatitis risk: Mendelian randomization study

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Shuai Yuan ◽  
Edward L. Giovannucci ◽  
Susanna C. Larsson
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Pancreatitis ◽  
Alcohol Consumption ◽  
Mendelian Randomization ◽  
Gallstone Disease ◽  
Smoking Initiation ◽  
Disease Type ◽  
Uk Biobank ◽  
Increased Risk

AbstractWe conducted a Mendelian randomization study to determine the potential causal associations of gallstone disease, diabetes, serum calcium, triglyceride levels, smoking and alcohol consumption with acute and chronic pancreatitis. Genetic variants associated with the exposures at p < 5 × 10−8 were selected from corresponding genome-wide association studies. Summary-level data for pancreatitis were obtained from the FinnGen consortium and UK Biobank. Univariable and multivariable Mendelian randomization analyses were performed and results from FinnGen and UK Biobank were combined using the fixed-effects meta-analysis method. Genetic predisposition to gallstone disease, type 2 diabetes and smoking initiation was associated with an increased risk of acute pancreatitis. The combined odds ratios (ORs) were 1.74 (95% confidence interval (CI), 1.57, 1.93) for gallstone disease, 1.14 (95% CI, 1.06, 1.21) for type 2 diabetes and 1.56 (95% CI, 1.32, 1.83) for smoking initiation. The association for type 2 diabetes attenuated after adjustment for gallstone disease. Genetic predisposition to gallstone disease and smoking initiation as well as higher genetically predicted serum calcium and triglyceride levels were associated with an increased risk of chronic pancreatitis. The combined ORs of chronic pancreatitis were 1.27 (95% CI, 1.08, 1.50) for gallstone disease, 1.86 (95% CI, 1.43, 2.43) for smoking initiation, 2.20 (95% CI, 1.30, 3.72) for calcium and 1.47 (95% CI, 1.23, 1.76) for triglycerides. This study provides evidence in support that gallstone disease, type 2 diabetes, smoking and elevated calcium and triglyceride levels are causally associated with the risk of acute or chronic pancreatitis.

Circulating adiponectin levels and systemic lupus erythematosus: a two-sample Mendelian randomization study

Rheumatology ◽  
2020 ◽  
Author(s):  
Yi-Lin Dan ◽  
Peng Wang ◽  
Zhongle Cheng ◽  
Qian Wu ◽  
Xue-Rong Wang ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Instrumental Variables ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Causal Effects ◽  
European Ancestry ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Inverse Variance ◽  
Weighted Median

Abstract Objectives Several studies have reported increased serum/plasma adiponectin levels in SLE patients. This study was performed to estimate the causal effects of circulating adiponectin levels on SLE. Methods We selected nine independent single-nucleotide polymorphisms that were associated with circulating adiponectin levels (P &lt; 5 × 10−8) as instrumental variables from a published genome-wide association study (GWAS) meta-analysis. The corresponding effects between instrumental variables and outcome (SLE) were obtained from an SLE GWAS analysis, including 7219 cases with 15 991 controls of European ancestry. Two-sample Mendelian randomization (MR) analyses with inverse-variance weighted, MR-Egger regression, weighted median and weight mode methods were used to evaluate the causal effects. Results The results of inverse-variance weighted methods showed no significantly causal associations of genetically predicted circulating adiponectin levels and the risk for SLE, with an odds ratio (OR) of 1.38 (95% CI 0.91, 1.35; P = 0.130). MR-Egger [OR 1.62 (95% CI 0.85, 1.54), P = 0.195], weighted median [OR 1.37 (95% CI 0.82, 1.35), P = 0.235) and weighted mode methods [OR 1.39 (95% CI 0.86, 1.38), P = 0.219] also supported no significant associations of circulating adiponectin levels and the risk for SLE. Furthermore, MR analyses in using SLE-associated single-nucleotide polymorphisms as an instrumental variable showed no associations of genetically predicted risk of SLE with circulating adiponectin levels. Conclusion Our study did not find evidence for a causal relationship between circulating adiponectin levels and the risk of SLE or of a causal effect of SLE on circulating adiponectin levels.

scholarly journals Causal relationships between genetically determined metabolites and human intelligence: A Mendelian randomization study

2020 ◽  
Author(s):  
Jian Yang ◽  
Binbin Zhao ◽  
Li Qian ◽  
Fengjie Gao ◽  
Yanjuan Fan ◽  
...  
Keyword(s):  
Complex Traits ◽  
Mendelian Randomization ◽  
Sensitivity Analyses ◽  
Human Intelligence ◽  
Causal Relationships ◽  
Biological Mechanisms ◽  
Inverse Variance ◽  
Weighted Median ◽  
Genetic And Environmental Factors ◽  
Genetically Determined

Abstract Intelligence predicts important life and health outcomes, but the biological mechanisms underlying differences in intelligence are not yet understood. The use of genetically determined metabotypes (GDMs) to understand the role of genetic and environmental factors, and their interactions, in human complex traits has been recently proposed. However, this strategy has not been applied to human intelligence. Here we implemented a two-sample Mendelian randomization (MR) analysis using GDMs to assess the causal relationships between genetically determined metabolites and human intelligence. The standard inverse-variance weighted (IVW) method was used for the primary MR analysis and three additional MR methods (MR-Egger, weighted median, and MR-PRESSO) were used for sensitivity analyses. Using 25 genetic variants as instrumental variables (IVs), our study found that 5-oxoproline was associated with better performance in human intelligence tests (P IVW = 9 · 25×10 -5 ). The causal relationship was robust when sensitivity analyses were applied (P MR-Egger = 0 · 0001, P Weighted median = 6 · 29×10 -6 , P MR-PRESSO = 0 · 0007), and no evidence of horizontal pleiotropy was observed. Similarly, also dihomo-linoleate (20:2n6) and p-acetamidophenylglucuronide showed robust association with intelligence. Our study provides novel insight by integrating genomics and metabolomics to estimate causal effects of genetically determined metabolites on human intelligence, which help to understanding of the biological mechanisms related to human intelligence.

scholarly journals Understanding the role of bitter taste perception in coffee, tea and alcohol consumption through Mendelian randomization

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Jue-Sheng Ong ◽  
Liang-Dar Hwang ◽  
Victor W. Zhong ◽  
Jiyuan An ◽  
Puya Gharahkhani ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Bitter Taste ◽  
Mendelian Randomization ◽  
Taste Perception

scholarly journals Causal relationships between genetically determined metabolites and human intelligence: a Mendelian randomization study

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jian Yang ◽  
Binbin Zhao ◽  
Li Qian ◽  
Fengjie Gao ◽  
Yanjuan Fan ◽  
...  
Keyword(s):  
Complex Traits ◽  
Mendelian Randomization ◽  
Sensitivity Analyses ◽  
Human Intelligence ◽  
Causal Relationships ◽  
Biological Mechanisms ◽  
Inverse Variance ◽  
Weighted Median ◽  
Genetic And Environmental Factors ◽  
Genetically Determined

AbstractIntelligence predicts important life and health outcomes, but the biological mechanisms underlying differences in intelligence are not yet understood. The use of genetically determined metabotypes (GDMs) to understand the role of genetic and environmental factors, and their interactions, in human complex traits has been recently proposed. However, this strategy has not been applied to human intelligence. Here we implemented a two-sample Mendelian randomization (MR) analysis using GDMs to assess the causal relationships between genetically determined metabolites and human intelligence. The standard inverse-variance weighted (IVW) method was used for the primary MR analysis and three additional MR methods (MR-Egger, weighted median, and MR-PRESSO) were used for sensitivity analyses. Using 25 genetic variants as instrumental variables (IVs), our study found that 5-oxoproline was associated with better performance in human intelligence tests (PIVW = 9.25 × 10–5). The causal relationship was robust when sensitivity analyses were applied (PMR-Egger = 0.0001, PWeighted median = 6.29 × 10–6, PMR-PRESSO = 0.0007), and repeated analysis yielded consistent result (PIVW = 0.0087). Similarly, also dihomo-linoleate (20:2n6) and p-acetamidophenylglucuronide showed robust association with intelligence. Our study provides novel insight by integrating genomics and metabolomics to estimate causal effects of genetically determined metabolites on human intelligence, which help to understanding of the biological mechanisms related to human intelligence.

scholarly journals Mendelian randomization analysis of the association between human blood cell traits and uterine polyps

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shuliu Sun ◽  
Yan Liu ◽  
Lanlan Li ◽  
Minjie Jiao ◽  
Yufen Jiang ◽  
...  
Keyword(s):  
Human Blood ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Random Effect ◽  
Sensitivity Analyses ◽  
Endometrial Polyps ◽  
Inverse Variance ◽  
Weighted Median ◽  
The Uk ◽  
Uterine Polyps

AbstractHuman blood cells (HBCs) play essential roles in multiple biological processes but their roles in development of uterine polyps are unknown. Here we implemented a Mendelian randomization (MR) analysis to investigate the effects of 36 HBC traits on endometrial polyps (EPs) and cervical polyps (CPs). The random-effect inverse-variance weighted method was adopted as standard MR analysis and three additional MR methods (MR-Egger, weighted median, and MR-PRESSO) were used for sensitivity analyses. Genetic instruments of HBC traits was extracted from a large genome-wide association study of 173,480 individuals, while data for EPs and CPs were obtained from the UK Biobank. All samples were Europeans. Using genetic variants as instrumental variables, our study found that both eosinophil count (OR 0.85, 95% CI 0.79–0.93, P = 1.06 × 10−4) and eosinophil percentage of white cells (OR 0.84, 95% CI 0.77–0.91, P = 2.43 × 10−5) were associated with decreased risk of EPs. The results were robust in sensitivity analyses and no evidences of horizontal pleiotropy were observed. While we found no significant associations between HBC traits and CPs. Our findings suggested eosinophils might play important roles in the pathogenesis of EPs. Besides, out study provided novel insight into detecting uterine polyps biomarkers using genetic epidemiology approaches.

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