scholarly journals The effect of education on adult mortality, health, and income: triangulating across genetic and policy reforms

2018 ◽  
Author(s):  
Neil M Davies ◽  
Matt Dickson ◽  
George Davey Smith ◽  
Frank Windmeijer ◽  
Gerard J van den Berg
Keyword(s):  
Genetic Variation ◽  
Life Expectancy ◽  
Mendelian Randomization ◽  
Policy Reform ◽  
Adult Mortality ◽  
Causal Effects ◽  
Natural Experiments ◽  
Policy Reforms ◽  
Sources Of Variation ◽  
The Uk

1AbstractOn average, educated people are healthier, wealthier and have higher life expectancy than those with less education. Numerous studies have attempted to determine whether these differences are caused by education, or are merely correlated with it and are ultimately caused by another factor. Previous studies have used a range of natural experiments to provide causal evidence. Here we exploit two natural experiments, perturbation of germline genetic variation associated with education which occurs at conception, known as Mendelian randomization, and a policy reform, the raising of the school leaving age in the UK in 1972. Previous studies have suggested that the differences in outcomes associated with education may be due to confounding. However, the two independent sources of variation we exploit largely imply consistent causal effects of education on outcomes much later in life.

scholarly journals Causal Associations Between Blood Lipids and COVID-19 Risk: A Two-Sample Mendelian Randomization Study

2021 ◽  
Author(s):  
Kun Zhang ◽  
Shan-Shan Dong ◽  
Yan Guo ◽  
Shi-Hao Tang ◽  
Hao Wu ◽  
...  
Keyword(s):  
Total Cholesterol ◽  
Blood Lipids ◽  
Mendelian Randomization ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Outcome Data ◽  
Causal Effects ◽  
Lipoprotein Cholesterol ◽  
Global Pandemic ◽  
The Uk

Objective: Coronavirus disease 2019 (COVID-19) is a global pandemic caused by the severe acute respiratory syndrome coronavirus 2. It has been reported that dyslipidemia is correlated with COVID-19, and blood lipids levels, including total cholesterol, HDL-C (high-density lipoprotein cholesterol), and LDL-C (low-density lipoprotein cholesterol) levels, were significantly associated with disease severity. However, the causalities of blood lipids on COVID-19 are not clear. Approach and Results: We performed 2-sample Mendelian randomization (MR) analyses to explore the causal effects of blood lipids on COVID-19 susceptibility and severity. Using the outcome data from the UK Biobank (1221 cases and 4117 controls), we observed potential positive causal effects of dyslipidemia (odds ratio [OR], 1.27 [95% CI, 1.08–1.49], P =3.18×10 −3 ), total cholesterol (OR, 1.19 [95% CI, 1.07–1.32], P =8.54×10 −4 ), and ApoB (apolipoprotein B; OR, 1.18 [95% CI, 1.07–1.29], P =1.01×10 −3 ) on COVID-19 susceptibility after Bonferroni correction. In addition, the effects of total cholesterol (OR, 1.01 [95% CI, 1.00–1.02], P =2.29×10 −2 ) and ApoB (OR, 1.01 [95% CI, 1.00–1.02], P =2.22×10 −2 ) on COVID-19 susceptibility were also identified using outcome data from the host genetics initiative (14 134 cases and 1 284 876 controls). Conclusions: In conclusion, we found that higher total cholesterol and ApoB levels might increase the risk of COVID-19 infection.

scholarly journals Novel insights into the consequences of obesity: a phenotype-wide Mendelian randomization study

2022 ◽  
Author(s):  
Chang He ◽  
Miaoran Zhang ◽  
Jiuling Li ◽  
Yiqing Wang ◽  
Lanlan Chen ◽  
...  
Keyword(s):  
Instrumental Variables ◽  
Fixed Effects ◽  
Mendelian Randomization ◽  
Portion Size ◽  
Causal Effects ◽  
Calorie Intake ◽  
Smoking Behaviors ◽  
Prostate Cancers ◽  
The Uk ◽  
Consequences Of Obesity

AbstractObesity is thought to significantly impact the quality of life. In this study, we sought to evaluate the health consequences of obesity on the risk of a broad spectrum of human diseases. The causal effects of exposing to obesity on health outcomes were inferred using Mendelian randomization (MR) analyses using a fixed effects inverse-variance weighted model. The instrumental variables were SNPs associated with obesity as measured by body mass index (BMI) reported by GIANT consortium. The spectrum of outcome consisted of the phenotypes from published GWAS and the UK Biobank. The MR-Egger intercept test was applied to estimate horizontal pleiotropic effects, along with Cochran’s Q test to assess heterogeneity among the causal effects of instrumental variables. Our MR results confirmed many putative disease risks due to obesity, such as diabetes, dyslipidemia, sleep disorder, gout, smoking behaviors, arthritis, myocardial infarction, and diabetes-related eye disease. The novel findings indicated that elevated red blood cell count was inferred as a mediator of BMI-induced type 2 diabetes in our bidirectional MR analysis. Intriguingly, the effects that higher BMI could decrease the risk of both skin and prostate cancers, reduce calorie intake, and increase the portion size warrant further studies. Our results shed light on a novel mechanism of the disease-causing roles of obesity.

scholarly journals Testosterone and longevity in men and women: A Mendelian randomization study in the UK Biobank

2020 ◽  
Author(s):  
CM Schooling ◽  
JV Zhao
Keyword(s):  
Sensitivity Analysis ◽  
Reproductive Success ◽  
Life Expectancy ◽  
Evolutionary Biology ◽  
Mendelian Randomization ◽  
Healthy Lifestyle ◽  
Smoking Initiation ◽  
Uk Biobank ◽  
Weighted Estimates ◽  
The Uk

AbstractBackgroundAfter decades of rising life expectancy, life expectancy in the developed West is currently stagnated and remains shorter in men than women. Very well-established evolutionary biology theory suggests that lifespan trades off against reproductive success, possibly sex-specifically. We examined whether a key driver of reproductive success, testosterone, affected lifespan using a Mendelian randomization study of longevity in the UK Biobank to obtain unbiased estimates, along with control exposures.MethodsWe applied published genetic instruments for testosterone to obtain inverse variance weighted estimates of associations with longevity, proxied by survival to (i.e., age at) recruitment, in 167020 men and 194174 women. We similarly obtained estimates for smoking initiation, and absorbate, a marker of vitamin C metabolism, because. We also conducted sensitivity analysis.ResultsOverall testosterone was associated with poorer survival (0.10 years younger at recruitment per effect size of testosterone, 95% confidence interval (CI) 0.004 to 0.20). As expected, smoking initiation was also associated with poorer survival (0.37 years younger, 95% CI 0.25 to 0.50), but not absorbate (0.01 years younger, 95% CI −0.09 to 0.11). Sensitivity analysis generally gave a similar interpretationConclusionsConsistent, with well-established theory, testosterone reduced longevity. Several aspects of a healthy lifestyle (such as a low animal fat diet) and several widely used medications (such as statins, metformin, dexamethasone and possibly aspirin) happen to modulate testosterone. Explicitly designing interventions sex-specifically based on these insights might be a means of addressing stagnating life expectancy and sexual disparities in life expectancy.

scholarly journals Investigating the association of testosterone with survival in men and women using a Mendelian randomization study in the UK Biobank

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
C. M. Schooling ◽  
J. V. Zhao
Keyword(s):  
Reproductive Success ◽  
Life Expectancy ◽  
Evolutionary Biology ◽  
Mendelian Randomization ◽  
Healthy Lifestyle ◽  
Smoking Initiation ◽  
Negative Control ◽  
Uk Biobank ◽  
Weighted Estimates ◽  
The Uk

AbstractLife expectancy in the developed West is currently stagnated and remains shorter in men than women. Well-established evolutionary biology theory suggests lifespan trades-off against reproductive success, possibly sex-specifically. We examined whether a key driver of reproductive success, testosterone, affected survival using a Mendelian randomization longevity study in the UK Biobank to obtain unbiased estimates, along with control exposures. We applied published genetic instruments for testosterone to obtain inverse variance weighted estimates of associations with survival to (i.e., age at) recruitment, in 167,020 men and 194,174 women. We similarly obtained estimates for a positive control (smoking initiation), and a negative control (absorbate), a marker of vitamin C metabolism. Testosterone was associated with poorer survival (0.10 years younger at recruitment per effect size of testosterone, 95% confidence interval (CI) 0.004 to 0.20). As expected, smoking initiation was also associated with poorer survival (0.37 years younger, 95% CI 0.25 to 0.50), but not absorbate (0.01 years younger, 95% CI − 0.09 to 0.11). Several aspects of a healthy lifestyle (low animal fat diet) and several widely used medications (statins, metformin, dexamethasone and possibly aspirin) may modulate testosterone. Explicitly designing interventions sex-specifically based on these insights might help address stagnating life expectancy and sexual disparities.

scholarly journals Phenome-wide investigation of the causal associations between childhood BMI and adult trait outcomes: a two-sample Mendelian randomization study

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Shan-Shan Dong ◽  
Kun Zhang ◽  
Yan Guo ◽  
Jing-Miao Ding ◽  
Yu Rong ◽  
...  
Keyword(s):  
Childhood Obesity ◽  
Dietary Habits ◽  
Mendelian Randomization ◽  
Later Life ◽  
Causal Effects ◽  
Inverse Variance ◽  
Weighted Median ◽  
Artery Disease ◽  
The Uk ◽  
Health Rating

Abstract Background Childhood obesity is reported to be associated with the risk of many diseases in adulthood. However, observational studies cannot fully account for confounding factors. We aimed to systematically assess the causal associations between childhood body mass index (BMI) and various adult traits/diseases using two-sample Mendelian randomization (MR). Methods After data filtering, 263 adult traits genetically correlated with childhood BMI (P < 0.05) were subjected to MR analyses. Inverse-variance weighted, MR-Egger, weighted median, and weighted mode methods were used to estimate the causal effects. Multivariable MR analysis was performed to test whether the effects of childhood BMI on adult traits are independent from adult BMI. Results We identified potential causal effects of childhood obesity on 60 adult traits (27 disease-related traits, 27 lifestyle factors, and 6 other traits). Higher childhood BMI was associated with a reduced overall health rating (β = − 0.10, 95% CI − 0.13 to − 0.07, P = 6.26 × 10−11). Specifically, higher childhood BMI was associated with increased odds of coronary artery disease (OR = 1.09, 95% CI 1.06 to 1.11, P = 4.28 × 10−11), essential hypertension (OR = 1.12, 95% CI 1.08 to 1.16, P = 1.27 × 10−11), type 2 diabetes (OR = 1.36, 95% CI 1.30 to 1.43, P = 1.57 × 10−34), and arthrosis (OR = 1.09, 95% CI 1.06 to 1.12, P = 8.80 × 10−9). However, after accounting for adult BMI, the detrimental effects of childhood BMI on disease-related traits were no longer present (P > 0.05). For dietary habits, different from conventional understanding, we found that higher childhood BMI was associated with low calorie density food intake. However, this association might be specific to the UK Biobank population. Conclusions In summary, we provided a phenome-wide view of the effects of childhood BMI on adult traits. Multivariable MR analysis suggested that the associations between childhood BMI and increased risks of diseases in adulthood are likely attributed to individuals remaining obese in later life. Therefore, ensuring that childhood obesity does not persist into later life might be useful for reducing the detrimental effects of childhood obesity on adult diseases.

scholarly journals A new Mendelian Randomization method to estimate causal effects of multivariable brain imaging exposures

2021 ◽  
Author(s):  
Chen Mo ◽  
Zhenyao Ye ◽  
Hongjie Ke ◽  
Tong Lu ◽  
Travis Canida ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Brain Imaging ◽  
Instrumental Variables ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Imaging Genetics ◽  
Causal Effects ◽  
Imaging Data ◽  
Multiple Exposures ◽  
The Uk

The advent of simultaneously collected imaging-genetics data in large study cohorts provides an unprecedented opportunity to assess the causal effect of brain imaging traits on externally measured experimental results (e.g., cognitive tests) by treating genetic variants as instrumental variables. However, classic Mendelian Randomization methods are limited when handling high-throughput imaging traits as exposures to identify causal effects. We propose a new Mendelian Randomization framework to jointly select instrumental variables and imaging exposures, and then estimate the causal effect of multivariable imaging data on the outcome. We validate the proposed method with extensive data analyses and compare it with existing methods. We further apply our method to evaluate the causal effect of white matter microstructure integrity on cognitive function. The findings suggest that our method achieved better performance regarding sensitivity, bias, and false discovery rate compared to individually assessing the causal effect of a single exposure and jointly assessing the causal effect of multiple exposures without dimension reduction. Our application results indicated that WM measures across different tracts have a joint causal effect that significantly impacts the cognitive function among the participants from the UK Biobank.

scholarly journals Welch-weighted Egger regression reduces false positives due to correlated pleiotropy in Mendelian randomization

2021 ◽  
Author(s):  
Brielin C Brown ◽  
David A Knowles
Keyword(s):  
Exploratory Data Analysis ◽  
Mendelian Randomization ◽  
False Positives ◽  
Causal Effects ◽  
Genetic Associations ◽  
Exploratory Data ◽  
Flexible Framework ◽  
The Uk ◽  
Modern Population ◽  
The Relationship

Modern population-scale biobanks contain simultaneous measurements of many phenotypes, providing unprecedented opportunity to study the relationship between biomarkers and disease. However, inferring causal effects from observational data is notoriously challenging. Mendelian randomization (MR) has recently received increased attention as a class of methods for estimating causal effects using genetic associations. However, standard methods result in pervasive false positives when two traits share a heritable, unobserved common cause. This is the problem of correlated pleiotropy. Here, we introduce a flexible framework for simulating traits with a common genetic confounder that generalizes recently proposed models, as well as simple approach we call Welch-weighted Egger regression (WWER) for estimating causal effects. We show in comprehensive simulations that our method substantially reduces false positives due to correlated pleiotropy while being fast enough to apply to hundreds of phenotypes. We first apply our method to a subset of the UK Biobank consisting of blood traits in inflammatorydisease, and then a broader set of 411 heritable phenotypes. We detect many effects with strong literaturesupport, as well as numerous behavioral effects that appear to stem from physician advice given to peopleat high risk for disease. We conclude that WWER is a powerful tool for exploratory data analysis inever-growing databases of genotypes and phenotypes

scholarly journals Causal effects from non-alcoholic fatty liver disease on kidney function: A Mendelian randomization study

2021 ◽  
Author(s):  
Sehoon Park ◽  
Soojin Lee ◽  
Yaerim Kim ◽  
Semin Cho ◽  
Kwangsoo Kim ◽  
...  
Keyword(s):  
Liver Disease ◽  
Kidney Function ◽  
Fatty Liver Disease ◽  
Mendelian Randomization ◽  
Negative Control ◽  
Causal Effects ◽  
European Ancestry ◽  
Uk Biobank ◽  
Low Probability ◽  
The Uk

AbstractBackground & aimsAn observational association between nonalcoholic fatty liver disease (NAFLD) and kidney function impairment has been reported. A genetic variant linked to an increased risk of NAFLD, the G allele of rs738409, has been reported to be associated with a reduction in estimated glomerular filtration rate (eGFR).Approach & ResultsIn this Mendelian randomization (MR) study, we first performed single-variant MR with rs738409 as a genetic instrument to predict NAFLD. Another genetic instrument was developed from a previous genome-wide association study for the NAFLD phenotype in the Million Veteran Program cohort among individuals of European ancestry (68,725 cases and 95,472 controls). The eGFR outcome was assessed in individuals of white British ancestry included in the UK Biobank (N = 321,405). Further, the associations were reassessed in two negative control subgroups (body mass index < 25 kg/m2 and serum alanine aminotransferase level < 20 IU/mL) with a low probability of developing NAFLD. As a replication analysis, a summary-level MR was performed with the European ancestry CKDGen dataset (N = 567,460). In the UK Biobank dataset, a genetic predisposition for NAFLD, either by rs738409 or a group of variants, was significantly associated with a reduced eGFR even with adjustment for major metabolic disorders. Although the associations were not significant in the negative control subgroups with a low probability of developing NAFLD, they were significant in the subgroups with a remaining risk of NAFLD, suggesting the absence of a horizontal pleiotropic pathway. The summary-level MR from the CKDGen dataset supported the causal effects of NAFLD on reduced eGFR.ConclusionsThis MR analysis supports the causal reduction in kidney function by NAFLD.

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.

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