Educational Attainment Decreases the Risk of COVID-19 Severity in the European Population: A Two-Sample Mendelian Randomization Study.
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ABSTRACT:
SUBMITTER: Yoshikawa M
PROVIDER: S-EPMC8212884 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background: Prior observational studies indicated that lower educational attainment (EA) is associated with higher COVID-19 risk, while these findings were vulnerable to bias from confounding factors. We aimed to clarify the causal effect of EA on COVID-19 susceptibility, hospitalization, and severity using Mendelian randomization (MR). Methods: We identified genetic instruments for EA from a large genome-wide association study (GWAS) (n = 1,131,881). Summary statistics for COVID-19 susceptibility (112,612 cases and 2,474,079 controls), hospitalization (24,274 cases and 2,061,529 controls), and severity (8,779 cases and 1,001,875 controls) were obtained from the COVID-19 Host Genetics Initiative. We used the single-variable MR (SVMR) and the multivariable MR (MVMR) controlling intelligence, income, body mass index, vigorous physical activity, sedentary behavior, smoking, and alcohol consumption to estimate the total and direct effects of EA on COVID-19 outcomes. Inverse variance weighted was the primary analysis method. All the statistical analyses were performed using R software. Results: Results from the SVMR showed that genetically predicted higher EA was correlated with a lower risk of COVID-19 susceptibility [odds ratio (OR) 0.86, 95% CI 0.84-0.89], hospitalization (OR 0.67, 95% CI 0.62-0.73), and severity (OR 0.67, 95% CI 0.58-0.79). EA still maintained its effects in most of the MVMR. Conclusion: Educational attainment is a predictor for susceptibility, hospitalization, and severity of COVID-19 disease. Population with lower EA should be provided with a higher prioritization to public health resources to decrease the morbidity and mortality of COVID-19.
| S-EPMC8732991 | biostudies-literature
Project description:This study aimed to investigate whether there is a causal relationship between educational attainment and delirium at the genetic level using the Mendelian randomization method, and provide new evidence for studies in this field. We found a causal relationship between educational attainment and delirium at the genetic level after excluding confounders using Mendelian randomization. The inverse variance weighting method of random effects was the main analysis method. The weighted median and Mendelian Randomization-Egger methods, as well as simple, and weighted modes were used as supplementary analysis methods. Additionally, horizontal pleiotropy tests were conducted, including the Mendelian Randomization-Egger intercept test and Mendelian Randomization Pleiotropy RESidual Sum and Outlier. Cochran's Q statistic was used to assess the size of heterogeneity. We retrieved all second single nucleotide polymorphism features and performed multivariate Mendelian randomization to adjust for the effect of potential confounders on our results. The inverse variance weighting suggested a negative correlation between genetically predicted educational attainment and delirium (0.67[0.49-0.92], p = 0.013); Mendelian Randomization Pleiotropy RESidual Sum and Outlier (0.67[0.49-0.92], p = 0.013) and multivariate Mendelian randomization (0.52[0.33-0.82], p = 0.005) results were generally consistent with the inverse variance weighting method. The Mendelian Randomization-Egger, simple, and weighted mode results were consistent with the inverse variance weighting results. Our results were not affected by pleiotropy or heterogeneity (p > 0.05, for both pleiotropy and heterogeneity). In addition, the "leave-one-out" analysis showed that the results of our Mendelian randomization analysis were not influenced by individual single nucleotide polymorphisms. Studies have found a causal relationship between educational attainment and delirium at the genetic level; higher educational attainment may be a protective factor against delirium. Clinically, more attention should be paid to patients at a high risk of delirium with low educational attainment.
| S-EPMC10988048 | biostudies-literature
Project description:Observational studies suggest that lower educational attainment (EA) may be associated with risky alcohol use behaviors; however, these findings may be biased by confounding and reverse causality. We performed two-sample Mendelian randomization (MR) using summary statistics from recent genome-wide association studies (GWAS) with >780,000 participants to assess the causal effects of EA on alcohol use behaviors and alcohol dependence (AD). Fifty-three independent genome-wide significant SNPs previously associated with EA were tested for association with alcohol use behaviors. We show that while genetic instruments associated with increased EA are not associated with total amount of weekly drinks, they are associated with reduced frequency of binge drinking ≥6 drinks (ßIVW = -0.198, 95% CI, -0.297 to -0.099, PIVW = 9.14 × 10-5), reduced total drinks consumed per drinking day (ßIVW = -0.207, 95% CI, -0.293 to -0.120, PIVW = 2.87 × 10-6), as well as lower weekly distilled spirits intake (ßIVW = -0.148, 95% CI, -0.188 to -0.107, PIVW = 6.24 × 10-13). Conversely, genetic instruments for increased EA were associated with increased alcohol intake frequency (ßIVW = 0.331, 95% CI, 0.267-0.396, PIVW = 4.62 × 10-24), and increased weekly white wine (ßIVW = 0.199, 95% CI, 0.159-0.238, PIVW = 7.96 × 10-23) and red wine intake (ßIVW = 0.204, 95% CI, 0.161-0.248, PIVW = 6.67 × 10-20). Genetic instruments associated with increased EA reduced AD risk: an additional 3.61 years schooling reduced the risk by ~50% (ORIVW = 0.508, 95% CI, 0.315-0.819, PIVW = 5.52 × 10-3). Consistency of results across complementary MR methods accommodating different assumptions about genetic pleiotropy strengthened causal inference. Our findings suggest EA may have important effects on alcohol consumption patterns and may provide potential mechanisms explaining reported associations between EA and adverse health outcomes.
| S-EPMC7182503 | biostudies-literature
Project description:Educational attainment has been associated with drinking behaviors in observation studies. We performed Mendelian randomization analysis to determine whether educational attainment causally affected drinking behaviors, including amount of alcohol intakes (in total and various types), drinking frequency, and drinking with or without meals among 334,507 white British participants from the UK Biobank cohort. We found that genetically instrumented higher education (1 additional year) was significantly related to higher total amount of alcohol intake (inverse-variance weighted method (IVW): beta = 0.44, 95% confidence interval (CI) 0.40-0.49, P = 1.57E-93). The causal relations with total amount and frequency of alcohol drinking were more evident among women. In analyses of different types of alcohol, higher educational attainment showed the strongest causal relation with more consumption of red wine (IVW beta = 0.34, 95% CI 0.32-0.36, P = 2.65E-247), followed by white wine/champagne, in a gender-specific manner. An inverse association was found for beer/cider and spirits. In addition, we found that 1 additional year of educational attainment was causally related to higher drinking frequency (IVW beta = 0.54, 95% CI 0.51-0.57, P = 4.87E-230) and a higher likelihood to take alcohol with meals (IVW: odds ratio (OR) = 3.10, 95% CI 2.93-3.29, P = 0.00E + 00). The results indicate causal relations of higher education with intake of more total alcohol especially red wine, and less beer/cider and spirits, more frequent drinking, and drinking with meals, suggesting the importance of improving drinking behaviors, especially among people with higher education.
| S-EPMC7246132 | biostudies-literature
Project description:Background: The association between educational attainment (EA) and offspring birth weight (BW) has been reported by several traditional epidemiological studies. However, evidence for this association tends to be mixed and confounded. This study aimed to investigate the causal association between EA of parents and offspring BW. Methods: Here, we carried out a two-sample bidirectional Mendelian randomization (MR) analysis to examine the causal association between EA of males (n = 131,695) and females (n = 162,028) and offspring BW using genetic instruments. Summary statistics of EA associated single nucleotide polymorphisms (SNPs) were extracted from a GWAS incorporating 293,723 individuals of European descent performed by the Social Science Genetic Association Consortium (SSGAC), and the effects of these SNPs on offspring BW were estimated using a GWAS meta-analysis of 86,577 participants of European descent from 25 studies. Univariable MR analyses were conducted using the inverse-variance weighted (IVW) method and four other methods. Further sensitivity analyses were carried out to test the viability of the results. Multivariable MR was used to examine the confounders between the exposure and outcome. Results: The result shows evidence that the offspring BW is positively causally affected by female EA. Each one standard deviation (SD) increase in female EA was associated with 0.24 SD higher of offspring BW (95% confidence interval [CI], 0.10 to 0.37, p < 0.001 for the IVW method). Similarly, change in offspring BW was 0.21 SD (95% CI: 0.07 to 0.34, p = 2.82 × 10-3) per one SD higher in male EA. No causal effect of BW on EA was found by any of the five methods. The causal association between female EA and offspring BW maintained after adjusting for alcoholic drinks per week and BMI. The effect of male EA on offspring BW was attenuated when we adjusted for BMI and alcoholic drinks per week using multivariable MR analysis. Conclusion: Our study indicated that female EA is positively causally associated with offspring BW. The association between male EA and offspring BW may be confounded by alcoholic drinks per week and BMI.
| S-EPMC9682907 | biostudies-literature
Project description:Higher educational attainment is observationally associated with lower risk of Alzheimer's disease. However, the biological mechanisms underpinning this association remain unclear. The protective effect of education on Alzheimer's disease may be mediated via increased brain reserve. We used two-sample Mendelian randomization to explore putative causal relationships between educational attainment, structural brain reserve as proxied by MRI phenotypes and Alzheimer's disease. Summary statistics were obtained from genome-wide association studies of educational attainment (n = 1 131 881), late-onset Alzheimer's disease (35 274 cases, 59 163 controls) and 15 measures of grey or white matter macro- or micro-structure derived from structural or diffusion MRI (nmax = 33 211). We conducted univariable Mendelian randomization analyses to investigate bidirectional associations between (i) educational attainment and Alzheimer's disease; (ii) educational attainment and imaging-derived phenotypes; and (iii) imaging-derived phenotypes and Alzheimer's disease. Multivariable Mendelian randomization was used to assess whether brain structure phenotypes mediated the effect of education on Alzheimer's disease risk. Genetically proxied educational attainment was inversely associated with Alzheimer's disease (odds ratio per standard deviation increase in genetically predicted years of schooling = 0.70, 95% confidence interval 0.60, 0.80). There were positive associations between genetically predicted educational attainment and four cortical metrics (standard deviation units change in imaging phenotype per one standard deviation increase in genetically predicted years of schooling): surface area 0.30 (95% confidence interval 0.20, 0.40); volume 0.29 (95% confidence interval 0.20, 0.37); intrinsic curvature 0.18 (95% confidence interval 0.11, 0.25); local gyrification index 0.21 (95% confidence interval 0.11, 0.31)]; and inverse associations with cortical intracellular volume fraction [-0.09 (95% confidence interval -0.15, -0.03)] and white matter hyperintensities volume [-0.14 (95% confidence interval -0.23, -0.05)]. Genetically proxied levels of surface area, cortical volume and intrinsic curvature were positively associated with educational attainment [standard deviation units change in years of schooling per one standard deviation increase in respective genetically predicted imaging phenotype: 0.13 (95% confidence interval 0.10, 0.16); 0.15 (95% confidence interval 0.11, 0.19) and 0.12 (95% confidence interval 0.04, 0.19)]. We found no evidence of associations between genetically predicted imaging-derived phenotypes and Alzheimer's disease. The inverse association of genetically predicted educational attainment with Alzheimer's disease did not attenuate after adjusting for imaging-derived phenotypes in multivariable analyses. Our results provide support for a protective causal effect of educational attainment on Alzheimer's disease risk, as well as potential bidirectional causal relationships between education and brain macro- and micro-structure. However, we did not find evidence that these structural markers affect risk of Alzheimer's disease. The protective effect of education on Alzheimer's disease may be mediated via other measures of brain reserve not included in the present study, or by alternative mechanisms.
| S-EPMC10151197 | biostudies-literature
Project description:Previous studies have been reported that the association between rheumatoid arthritis (RA) and breast cancer remains inconclusive. A two-sample Mendelian randomization (MR) analysis can reveal the potential causal association between exposure and outcome. A two-sample MR analysis using the penalized robust inverse variance weighted (PRIVW) method was performed to analyze the association between RA and breast cancer risk based on the summary statistics of six genome-wide association studies (GWAS) targeting RA in an East Asian population along with summary statistics of the BioBank Japan (BBJ), Breast Cancer Association Consortium (BCAC), and Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) targeting breast cancer. We found that the direction of the effect of RA on breast cancer varied among GWAS-summary data from BBJ, BCAC, and CIMBA. Significant horizontal pleiotropy based on a penalized robust MR-Egger regression was observed only for BBJ and CIMBA BRCA2 carriers. As the results of the two-sample MR analyses were inconsistent, the causal association between RA and breast cancer was inconclusive. The biological mechanisms explaining the relationship between RA and breast cancer were unclear in Asian as well as in Caucasians. Further studies using large-scale patient cohorts are required for the validation of these results.
| S-EPMC7694331 | biostudies-literature
Project description:Asthma is a common chronic respiratory disease. In the past 10 years, genome-wide association study (GWAS) has been widely used to identify the common asthma genetic variants. Importantly, these publicly available asthma GWAS datasets provide important data support to investigate the causal association of kinds of risk factors with asthma by a Mendelian randomization (MR) design. It is known that socioeconomic status is associated with asthma. However, it remains unclear about the causal association between socioeconomic status and asthma. Here, we selected 162 independent educational attainment genetic variants as the potential instruments to evaluate the causal association between educational attainment and asthma using large-scale GWAS datasets of educational attainment (n = 405,072) and asthma (n = 30,810). We conducted a pleiotropy analysis using the MR-Egger intercept test and the MR pleiotropy residual sum and outlier (MR-PRESSO) test. We performed an MR analysis using inverse-variance weighted, weighted median, MR-Egger, and MR-PRESSO. The main analysis method inverse-variance weighted indicated that each 1 standard deviation increase in educational attainment (3.6 years) could reduce 35% asthma risk [odds ratio (OR) = 0.65, 95% confidence interval (CI) 0.51-0.85, P = 0.001]. Importantly, evidence from other MR methods further supported this finding, including weighted median (OR = 0.55, 95% CI 0.38-0.80, P = 0.001), MR-Egger (OR = 0.48, 95% CI 0.16-1.46, P = 0.198), and MR-PRESSO (OR = 0.65, 95% CI 0.51-0.85, P = 0.0015). Meanwhile, we provide evidence to support that educational attainment protects against asthma risk dependently on cognitive performance using multivariable MR analysis. In summary, we highlight the protective role of educational attainment against asthma. Our findings may have public health applications and deserve further investigation.
| S-EPMC8381375 | biostudies-literature
Project description:BackgroundPrevious studies have found that children born with a non-syndromic orofacial cleft have lower-than-average educational attainment. Differences could be due to a genetic predisposition to low intelligence and academic performance, factors arising due to the cleft phenotype (such as social stigmatization, impaired speech/language development) or confounding by the prenatal environment. A clearer understanding of this mechanism will inform interventions to improve educational attainment in individuals born with a cleft, which could substantially improve their quality of life. We assessed evidence for the hypothesis that common variant genetic liability to non-syndromic cleft lip with or without cleft palate (nsCL/P) influences educational attainment.MethodsWe performed a genome-wide association study (GWAS) meta-analysis of nsCL/P with 1692 nsCL/P cases and 4259 parental and unrelated controls. Using GWAS summary statistics, we performed Linkage Disequilibrium (LD)-score regression to estimate the genetic correlation between nsCL/P, educational attainment (GWAS n = 766 345) and intelligence (GWAS n = 257 828). We used two-sample Mendelian randomization to evaluate the causal effects of genetic liability to nsCL/P on educational attainment and intelligence.ResultsThere was limited evidence for shared genetic aetiology or causal relationships between nsCL/P and educational attainment [genetic correlation (rg) -0.05, 95% confidence interval (CI) -0.12 to 0.01, P 0.13; MR estimate (βMR) -0.002, 95% CI -0.009 to 0.006, P 0.679) or intelligence (rg -0.04, 95% CI -0.13 to 0.04, P 0.34; βMR -0.009, 95% CI -0.02 to 0.002, P 0.11).ConclusionsCommon variants are unlikely to predispose individuals born with nsCL/P to low educational attainment or intelligence. This is an important first step towards understanding the aetiology of low educational attainment in this group.
| S-EPMC7660147 | biostudies-literature
Project description:BackgroundInfertility affects many couples globally, causing physical, emotional, and financial burdens. While observational studies suggest a link between psychiatric disorders and female infertility, causal relationships remain uncertain. Mendelian randomization analysis, using genome-wide association studies data, minimizes confounding factors and reverse causation, providing valuable insights into causal associations.MethodsWe conducted Mendelian randomization analysis to explore the potential causal relationship between female infertility and psychiatric disorders. Genome-wide association studies summary data for female infertility (112,105 individuals of European ancestry, comprising 11,442 cases and 100,663 controls), depression (807,553 individuals of European ancestry, comprising 246,363 cases and 561,190 controls), anxiety (21,763 individuals of European ancestry, comprising 7,016 cases and 14,745 controls), bipolar disorder (51,710 individuals of European ancestry, comprising 20,352 cases and 31,358 controls), and eating disorders (72,517 individuals of European ancestry, comprising 16,992 cases and 55,525 controls) were utilized. Instrumental variables were selected based on significant single nucleotide polymorphisms associated with each phenotype. We assessed instrumental variable strength, examined confounding factors, and employed inverse variance weighting, weighted median, and MR-Egger approaches for analysis.ResultsOur analysis included 85 single nucleotide polymorphisms for female infertility and 62 single nucleotide polymorphisms for psychiatric disorders. Results suggest a potential causal relationship between depression and female infertility, with both inverse variance weighting and weighted median methods showing increased infertility risk in depressed patients. Evidence is weak regarding bipolar disorder not increasing female infertility risk. We found no evidence supporting causal links between anxiety, eating disorders, and female infertility. Similarly, no causal relationship was found between female infertility and psychiatric disorders in the opposite direction. Sensitivity analyses and tests for heterogeneity and polymorphism supported result robustness.ConclusionsThis analysis provides evidence for a potential causal relationship between depression and female infertility. Addressing depression in infertile women may improve fertility outcomes. Further research is needed to explore underlying mechanisms and potential interventions for improving fertility outcomes in women with psychiatric disorders.
| S-EPMC10797979 | biostudies-literature