Educational attainment protects against type 2 diabetes independently of cognitive performance: a Mendelian randomization study

Liang, Jialin; Cai, Huan; Liang, Ganxiong; Z, Liu; Liang, Fang Ting; Zhu, Bo; Liu, Baoying; Zhang, Hao

doi:10.1007/s00592-020-01647-w

Cited by 18 publications

(17 citation statements)

References 37 publications

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“…Hence, all these findings discussed earlier indicated that educational attainment had causal effects on the risk of epilepsy (Wang et al, 2021), coronary heart disease (Gill et al, 2019), stroke (Gill et al, 2019), type 2 diabetes (Liang et al, 2021), and suicide attempt (Rosoff et al, 2020), independently of cognitive performance. However, the causal effect of educational attainment on the risk of Alzheimer's disease may be mediated by cognitive performance (Anderson et al, 2020).…”

Section: Discussionmentioning

confidence: 82%

“…Carter et al (2019) found that BMI, systolic blood pressure, and smoking behavior could mediate the protective role of education on the risk of cardiovascular outcomes, including coronary heart disease, stroke, myocardial infarction, and cardiovascular disease (all subtypes; all measured in OR). Liang et al (2021) identified that educational attainment protected against type 2 diabetes independently of cognitive performance. Rosoff et al (2020) found that educational attainment could reduce the risk of suicide attempts in individuals with and without psychiatric disorders independent of cognition.…”

Section: Discussionmentioning

confidence: 99%

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Evaluating the Causal Association Between Educational Attainment and Asthma Using a Mendelian Randomization Design

Chen

Shiyao

et al. 2021

Front. Genet.

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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.

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Evaluating the Causal Association Between Educational Attainment and Asthma Using a Mendelian Randomization Design

Chen

Shiyao

et al. 2021

Front. Genet.

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“…Recently, a large-scale genome-wide association study (GWAS) identified genetic variants associated with EA (20), which provides high-quality genetic instruments for us to estimate the causal effects of EA on health outcomes. The genetic variants derived from this GWAS have already been used to evaluate the causal effects of EA on osteoarthritis (21) and diabetes (22).…”

Section: Introductionmentioning

confidence: 99%

Causal Associations Between Educational Attainment and 14 Urological and Reproductive Health Outcomes: A Mendelian Randomization Study

Wang

Jian

Gao

et al. 2021

Front. Public Health

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Background: The impact of educational attainment (EA) on multiple urological and reproductive health outcomes has been explored in observational studies. Here we used Mendelian randomization (MR) to investigate whether EA has causal effects on 14 urological and reproductive health outcomes.Methods: We obtained summary statistics for EA and 14 urological and reproductive health outcomes from genome-wide association studies (GWAS). MR analyses were applied to explore the potential causal association between EA and them. Inverse variance weighted was the primary analytical method.Results: Genetically predicted one standard deviation (SD) increase in EA was causally associated with a higher risk of prostate cancer [odds ratio (OR) 1.14, 95% confidence interval (CI) 1.05–1.25, P = 0.003] and a reduced risk of kidney stone (OR 0.73, 95% CI 0.62–0.87, P < 0.001) and cystitis (OR 0.76, 95% CI 0.67–0.86, P < 0.001) after Bonferroni correction. EA was also suggestively correlated with a lower risk of prostatitis (OR 0.76, 95% CI 0.59–0.98, P = 0.037) and incontinence (OR 0.64, 95% CI 0.47–0.87, P = 0.004). For the bioavailable testosterone levels and infertility, sex-specific associations were observed, with genetically determined increased EA being related to higher levels of testosterone in men (β 0.07, 95% CI 0.04–0.10, P < 0.001), lower levels of testosterone in women (β −0.13, 95% CI−0.16 to−0.11, P < 0.001), and a lower risk of infertility in women (OR 0.74, 95% CI 0.64–0.86, P < 0.001) but was not related to male infertility (OR 0.79, 95% CI 0.52–1.20, P = 0.269) after Bonferroni correction. For bladder cancer, kidney cancer, testicular cancer, benign prostatic hyperplasia, and erectile dysfunction, no causal effects were observed.Conclusions: EA plays a vital role in urological diseases, especially in non-oncological outcomes and reproductive health. These findings should be verified in further studies when GWAS data are sufficient.

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“…We assume that the effect direction is from educational attainment to HbA1c level since the exposure has remained unchanged during the study and was collected before measuring HbA1c. Moreover, previous research has reported potential causality between educational attainment and type 2 diabetes [38]. In addition, educational attainment is associated with DNAm [39], and DNAm is also associated with HbA1c [40].…”

Section: Data Example Using Mesa: Study Design and Methodsmentioning

confidence: 94%

Methods for Large-scale Single Mediator Hypothesis Testing: Possible Choices and Comparisons

Du¹,

Zhou²,

Wu³

et al. 2022

Preprint

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Mediation hypothesis testing for a large number of mediators is challenging due to the composite structure of the null hypothesis, H 0 : αβ = 0 (α: effect of the exposure on the mediator after adjusting for confounders; β: effect of the mediator on the outcome after adjusting for exposure and confounders). In this paper, we reviewed three classes of methods for multiple mediation hypothesis testing. In addition to these existing methods, we developed the Sobel-comp method, which uses a corrected mixture reference distribution for Sobel's test statistic. We performed extensive simulation studies to compare all six methods in terms of the false positive rates under the null hypothesis and the true positive rates under the alternative hypothesis. We found that the class of methods which uses a mixture reference distribution could best maintain the false positive rates at the nominal level under the null hypothesis and had the greatest true positive rates under the alternative hypothesis. We applied all methods to study the mediation mechanism of DNA methylation sites in the pathway from adult socioeconomic status to glycated hemoglobin level using data from the Multi-Ethnic Study of Atherosclerosis (MESA). We also provide guidelines for choosing the optimal mediation hypothesis testing method in practice. (word count: 196)

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Educational attainment protects against type 2 diabetes independently of cognitive performance: a Mendelian randomization study

Cited by 18 publications

References 37 publications

Evaluating the Causal Association Between Educational Attainment and Asthma Using a Mendelian Randomization Design

Evaluating the Causal Association Between Educational Attainment and Asthma Using a Mendelian Randomization Design

Causal Associations Between Educational Attainment and 14 Urological and Reproductive Health Outcomes: A Mendelian Randomization Study

Methods for Large-scale Single Mediator Hypothesis Testing: Possible Choices and Comparisons

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