scholarly journals Education Attainment, Intelligence and COVID-19: A Mendelian Randomization Study

2021 ◽  
Vol 10 (21) ◽  
pp. 4870
Author(s):  
Gloria Hoi-Yee Li ◽  
Stanley Kam-Ki Lam ◽  
Ian Chi-Kei Wong ◽  
Jody Kwok-Pui Chu ◽  
Ching-Lung Cheung
Keyword(s):  
Higher Education ◽  
Mendelian Randomization ◽  
Meta Analysis ◽  
Multivariable Analysis ◽  
Education Attainment ◽  
Genome Wide ◽  
Higher Education Attainment ◽  
Lower Education ◽  
Genetically Determined ◽  
Reduced Risk

Background: Evidence of socioeconomic inequality in COVID-19-related outcomes is emerging, with a higher risk of infection and mortality observed among individuals with lower education attainment. We aimed to evaluate the potential interventions against COVID-19 from the socioeconomic perspective, including improvement in education and intelligence. Methods: With a two-sample Mendelian randomization approach using summary statistics from the largest genome-wide association meta-analysis, univariable analysis was adopted to evaluate the total causal effects of genetically determined education attainment and intelligence on COVID-19 outcomes. Multivariable analysis was performed to dissect the potential mechanisms. Results: Genetic predisposition to higher education attainment by 1 SD (4.2 years) was independently associated with reduced risk of COVID-19 severity (OR = 0.508 [95% CI: 0.417–0.617]; p < 0.001). Genetically higher education attainment also lowered the risk of COVID-19 hospitalization (0.685 [0.593–0.791]; p < 0.001), but the association was attenuated after adjustment for beta estimates of intelligence in multivariable analysis. Genetically higher intelligence was associated with reduced risk of COVID-19 hospitalization (0.780 [0.655–0.930]; p = 0.006), with attenuation of association after adjustment for education attainment. Null association was observed for genetically determined education attainment and intelligence with SARS-CoV-2 infection. Conclusion: Education may act independently and jointly with intelligence in improving the COVID-19 outcomes. Improving education may potentially alleviate the COVID-19-related health inequality.

scholarly journals Causal effects of education on chronic kidney disease: a Mendelian randomization study

2020 ◽  
Author(s):  
Sehoon Park ◽  
Soojin Lee ◽  
Yaerim Kim ◽  
Yeonhee Lee ◽  
Min Woo Kang ◽  
...  
Keyword(s):  
Higher Education ◽  
Mendelian Randomization ◽  
Meta Analysis ◽  
Causal Effects ◽  
Genome Wide Association ◽  
Uk Biobank ◽  
Education Attainment ◽  
Genome Wide ◽  
Higher Education Attainment ◽  
The Uk

Abstract Background Poor socio-economic status, including low education attainment, has been reported in chronic kidney disease (CKD) patients. We aimed to investigate the causal effects of education attainment on the risk of CKD. Methods The study was an observational cohort study including Mendelian randomization (MR) analysis. First, the clinical association between education attainment years as the exposure and prevalent CKD Stages 3–5 as the outcome was investigated by multivariable logistic regression in 308 741 individuals 40–69 years of age from the UK Biobank. MR analysis was performed with a previously reported genetic instrument from a genome-wide association meta-analysis of education attainment. Two-sample MR was performed with summary statistics for CKD in 567 460 individuals with European ancestry in the CKDGen genome-wide association meta-analysis. The findings were replicated by allele score–based MR in 321 260 individuals of white British ancestry in the UK Biobank with quality-controlled genetic data. Results Higher education attainment was significantly associated with lower adjusted odds for CKD in the clinical analysis {&gt;17 years versus &lt;16 years, adjusted odds ratio [OR] 0.910 [95% confidence interval (CI) 0.849–0.975]}. The causal estimates obtained by the inverse variance method in the two-sample MR indicated that higher genetically predicted education attainment causally reduced the risk of CKD [OR 0.934 (95% CI 0.873–0.999)]. Allele score–based MR also supported that higher education attainment was causally linked to a decreased risk of CKD [adjusted OR 0.944 (95% CI 0.922–0.966)]. Conclusion The study suggests that higher education attainment causally reduces the risk of CKD development in the general population.

scholarly journals Causal effect of renal function on venous thromboembolism: a two-sample Mendelian randomization investigation

2021 ◽  
Author(s):  
Shuai Yuan ◽  
Maria Bruzelius ◽  
Susanna C. Larsson
Keyword(s):  
Renal Function ◽  
Venous Thromboembolism ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Meta Analysis ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
Genome Wide ◽  
Increased Risk ◽  
Mr Study

AbstractWhether renal function is causally associated with venous thromboembolism (VTE) is not yet fully elucidated. We conducted a two-sample Mendelian randomization (MR) study to determine the causal effect of renal function, measured as estimated glomerular filtration rate (eGFR), on VTE. Single-nucleotide polymorphisms associated with eGFR were selected as instrumental variables at the genome-wide significance level (p < 5 × 10−8) from a meta-analysis of 122 genome-wide association studies including up to 1,046,070 individuals. Summary-level data for VTE were obtained from the FinnGen consortium (6913 VTE cases and 169,986 non-cases) and UK Biobank study (4620 VTE cases and 356,574 non-cases). MR estimates were calculated using the random-effects inverse-variance weighted method and combined using fixed-effects meta-analysis. Genetically predicted decreased eGFR was significantly associated with an increased risk of VTE in both FinnGen and UK Biobank. For one-unit decrease in log-transformed eGFR, the odds ratios of VTE were 2.93 (95% confidence interval (CI) 1.25, 6.84) and 4.46 (95% CI 1.59, 12.5) when using data from FinnGen and UK Biobank, respectively. The combined odds ratio was 3.47 (95% CI 1.80, 6.68). Results were consistent in all sensitivity analyses and no horizontal pleiotropy was detected. This MR-study supported a casual role of impaired renal function in VTE.

Associations of observational and genetically determined caffeine intake with coronary artery disease and diabetes

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Said ◽  
Y.J Van De Vegte ◽  
N Verweij ◽  
P Van Der Harst
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Mendelian Randomization ◽  
Cox Regression ◽  
Caffeine Intake ◽  
Uk Biobank ◽  
Genome Wide ◽  
Artery Disease ◽  
Genetically Determined

Abstract Background Caffeine is the most widely consumed psychostimulant and is associated with lower risk of coronary artery disease (CAD) and type 2 diabetes (T2D). However, whether these associations are causal remains unknown. Objectives This study aimed to identify genetic variants associated with caffeine intake, and to investigate possible causal links between genetically determined caffeine intake and CAD or T2D. Additionally, we aimed to replicate previous observational findings between caffeine intake and CAD or T2D. Methods Genome wide associated studies (GWAS) were performed on caffeine intake from coffee, tea or both in 407,072 UK Biobank participants. Identified variants were used in a two-sample Mendelian randomization (MR) approach to investigate evidence for causal links between caffeine intake and CAD in CARDIoGRAMplusC4D (60,801 cases; 123,504 controls) or T2D in DIAGRAM (26,676 cases; 132,532 controls). Observational associations were tested within UK Biobank using Cox regression analyses. Results Moderate observational caffeine intakes from coffee or tea were associated with lower risks of CAD or T2D compared to no or high intake, with the lowest risks at intakes of 120–180 mg/day from coffee for CAD (HR=0.77 [95% CI: 0.73–0.82; P&lt;1e-16]), and 300–360 mg/day for T2D (HR=0.76 [95% CI: 0.67–0.86]; P=1.57e-5). GWAS identified 51 novel genetic loci associated with caffeine intake, enriched for central nervous system genes. In contrast to observational analyses, MR analyses in CARDIoGRAMplusC4D and DIAGRAM yielded no evidence for causal links between caffeine intake and the development of CAD or T2D. Conclusions MR analyses indicate caffeine intake might not protect against CAD or T2D, despite protective associations in observational analyses. Manhattan_plot_CaffeineIntake Funding Acknowledgement Type of funding source: None

Disrupted daily routines mediate the socioeconomic gradient of depression amid public health crises: A repeated cross-sectional study

2021 ◽  
pp. 000486742110512
Author(s):  
Francisco Tsz Tsun Lai ◽  
Vivien Kin Yi Chan ◽  
Tsz Wai Li ◽  
Xue Li ◽  
Stevan E Hobfoll ◽  
...  
Keyword(s):  
Higher Education ◽  
Logistic Regression ◽  
Hong Kong ◽  
Daily Routine ◽  
Education Attainment ◽  
Mediating Role ◽  
Socioeconomic Gradient ◽  
Higher Education Attainment ◽  
Probable Depression

Objective: There is a socioeconomic gradient to depression risks, with more pronounced inequality amid macroenvironmental potential traumatic events. Between mid-2019 and mid-2020, the Hong Kong population experienced drastic societal changes, including the escalating civil unrest and the COVID-19 pandemic. We examined the change of the socioeconomic gradient in depression and the potential intermediary role of daily routine disruptions. Method: We conducted repeated territory-wide telephone surveys in July 2019 and July 2020 with 1112 and 2034 population-representative Cantonese-speaking Hong Kong citizens above 15 years old, respectively. Stratified by year, we examined the association between socioeconomic indicators (education attainment, household income, employment status and marital status) and probable depression (nine-item Patient Health Questionnaire [PHQ-9] ⩾ 10) using logistic regression. Differences in the socioeconomic gradient between 2019 and 2020 were tested. Finally, we performed a path analysis to test for the mediating role of daily routine disruptions. Results: Logistic regression showed that higher education attainment in 2019 and being married in 2020 were protective against probable depression. Interaction analysis showed that the inverse association of higher education attainment with probable depression attenuated in 2020 but that of being married increased. Path analysis showed that the mediated effects through daily routine disruptions accounted for 95.9% of the socioeconomic gradient of probable depression in 2020, compared with 13.1% in 2019. Conclusion: From July 2019 to July 2020, the mediating role of daily routine disruptions in the socioeconomic gradient of depression in Hong Kong increased. It is thus implied that infection control measures should consider the relevant potential mental health impacts accordingly.

scholarly journals A genome-wide association study identifies new loci for factor VII and implicates factor VII in ischemic stroke etiology

Blood ◽  
2019 ◽  
Vol 133 (9) ◽  
pp. 967-977 ◽  
Author(s):  
Paul S. de Vries ◽  
Maria Sabater-Lleal ◽  
Jennifer E. Huffman ◽  
Jonathan Marten ◽  
Ci Song ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
Coagulation Cascade ◽  
Factor Vii ◽  
Phenotypic Variance ◽  
Genome Wide ◽  
Huh7 Cells

Abstract Factor VII (FVII) is an important component of the coagulation cascade. Few genetic loci regulating FVII activity and/or levels have been discovered to date. We conducted a meta-analysis of 9 genome-wide association studies of plasma FVII levels (7 FVII activity and 2 FVII antigen) among 27 495 participants of European and African ancestry. Each study performed ancestry-specific association analyses. Inverse variance weighted meta-analysis was performed within each ancestry group and then combined for a trans-ancestry meta-analysis. Our primary analysis included the 7 studies that measured FVII activity, and a secondary analysis included all 9 studies. We provided functional genomic validation for newly identified significant loci by silencing candidate genes in a human liver cell line (HuH7) using small-interfering RNA and then measuring F7 messenger RNA and FVII protein expression. Lastly, we used meta-analysis results to perform Mendelian randomization analysis to estimate the causal effect of FVII activity on coronary artery disease, ischemic stroke (IS), and venous thromboembolism. We identified 2 novel (REEP3 and JAZF1-AS1) and 6 known loci associated with FVII activity, explaining 19.0% of the phenotypic variance. Adding FVII antigen data to the meta-analysis did not result in the discovery of further loci. Silencing REEP3 in HuH7 cells upregulated FVII, whereas silencing JAZF1 downregulated FVII. Mendelian randomization analyses suggest that FVII activity has a positive causal effect on the risk of IS. Variants at REEP3 and JAZF1 contribute to FVII activity by regulating F7 expression levels. FVII activity appears to contribute to the etiology of IS in the general population.

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