scholarly journals Does smoking cause lower educational attainment and general cognitive ability? Triangulation of causal evidence using multiple study designs

2020 ◽  
pp. 1-9
Author(s):  
Suzanne H. Gage ◽  
Hannah M. Sallis ◽  
Glenda Lassi ◽  
Robyn E. Wootton ◽  
Claire Mokrysz ◽  
...  
Keyword(s):  
Educational Attainment ◽  
Cognitive Ability ◽  
Fluid Intelligence ◽  
Causal Effect ◽  
Smoking Initiation ◽  
Sensitivity Analyses ◽  
Mendelian Randomisation ◽  
General Cognitive Ability ◽  
Inverse Variance ◽  
Lower Educational Attainment

Abstract Background Observational studies have found associations between smoking and both poorer cognitive ability and lower educational attainment; however, evaluating causality is challenging. We used two complementary methods to explore this. Methods We conducted observational analyses of up to 12 004 participants in a cohort study (Study One) and Mendelian randomisation (MR) analyses using summary and cohort data (Study Two). Outcome measures were cognitive ability at age 15 and educational attainment at age 16 (Study One), and educational attainment and fluid intelligence (Study Two). Results Study One: heaviness of smoking at age 15 was associated with lower cognitive ability at age 15 and lower educational attainment at age 16. Adjustment for potential confounders partially attenuated findings (e.g. fully adjusted cognitive ability β −0.736, 95% CI −1.238 to −0.233, p = 0.004; fully adjusted educational attainment β −1.254, 95% CI −1.597 to −0.911, p < 0.001). Study Two: MR indicated that both smoking initiation and lifetime smoking predict lower educational attainment (e.g. smoking initiation to educational attainment inverse-variance weighted MR β −0.197, 95% CI −0.223 to −0.171, p = 1.78 × 10−49). Educational attainment results were robust to sensitivity analyses, while analyses of general cognitive ability were less so. Conclusion We find some evidence of a causal effect of smoking on lower educational attainment, but not cognitive ability. Triangulation of evidence across observational and MR methods is a strength, but the genetic variants associated with smoking initiation may be pleiotropic, suggesting caution in interpreting these results. The nature of this pleiotropy warrants further study.

scholarly journals Does Smoking Cause Lower Educational Attainment and General Cognitive Ability? Triangulation of causal evidence using multiple study designs

2019 ◽  
Author(s):  
Suzanne H. Gage ◽  
Hannah Sallis ◽  
Glenda Lassi ◽  
Robyn Wootton ◽  
Claire Mokrysz ◽  
...  
Keyword(s):  
Cohort Study ◽  
Educational Attainment ◽  
Cognitive Ability ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Smoking Initiation ◽  
Sensitivity Analyses ◽  
Genome Wide Association Studies ◽  
Summary Statistics ◽  
Lower Educational Attainment

AbstractObjectivesObservational epidemiological studies have found associations between smoking and both poorer cognitive ability and lower educational attainment; however, evaluating causality is more challenging. We used two complementary methods to attempt to ascertain whether smoking causes poorer cognitive ability and lower educational attainment.DesignA cohort study (Study One) and a two-sample Mendelian randomization study using publicly-available summary statistics (Study Two).SettingThe Avon Longitudinal Study of Parents and Children (ALSPAC), a birth-cohort study based in Bristol, United Kingdom, and general population samples from published genome-wide association studies (GWAS).ParticipantsUp to 12,004 young people in ALSPAC (complete case analysis N = 2,107) (Study One and Study Two), and summary statistics from three previously published GWAS (not individual-level data) (Study Two).Main outcome measuresCognitive ability at age 15 (assessed via the Wechsler Abbreviated Scale of Intelligence) and educational attainment at age 16 (assessed via school records) (Study One), and educational attainment (measured as years in education) and fluid intelligence from previously published GWAS (Study Two).ResultsIn Study One, heaviness of smoking at age 15 was associated with lower cognitive ability at age 15 and lower educational attainment at age 16. Adjustment for potential confounders and earlier cognitive ability or educational attainment attenuated findings although evidence of an association remained (e.g., fully adjusted cognitive ability beta - 0.736, 95% CI −1.238 to −0.233, P = 0.004; fully adjusted educational attainment beta −1.254, 95% CI −1.597 to −0.911, P < 0.001). Comparable results were found in sensitivity analyses of multiply imputed data. In Study Two, two-sample Mendelian randomization indicated that both smoking initiation and lifetime smoking lower educational attainment and cognitive ability (e.g., smoking initiation to educational attainment inverse-variance weighted MR beta −0.197, 95% CI −0.223, −0.171, P = 1.78 × 10−49). Educational attainment results were robust to various sensitivity analyses, while cognition analyses were less so.ConclusionsOur results provide evidence consistent with a causal effect of smoking on lower educational attainment, although were less consistent for cognitive ability. The triangulation of evidence from observational and Mendelian randomisation methods is an important strength for causal inference.Summary boxesWhat is already known on this topicAssociations are seen between smoking and both educational attainment and cognition. These is some evidence that educational attainment might causally influence smoking, but causality in the opposite direction has not been assessed.What this study addsUsing multiple methodologies, we found evidence consistent with a causal effect of smoking on lower educational attainment. An exploration of potential mechanisms could inform the development of interventions to mitigate this risk.

scholarly journals The causal effect of educational attainment on Alzheimer’s disease: A two-sample Mendelian randomization study

2017 ◽  
Author(s):  
Emma L Anderson ◽  
Kaitlin H Wade ◽  
Gibran Hemani ◽  
Jack Bowden ◽  
Roxanna Korologou-Linden ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Educational Attainment ◽  
Genome Wide Association Study ◽  
Causal Effect ◽  
Sensitivity Analyses ◽  
Nucleotide Polymorphisms ◽  
Inverse Variance ◽  
Higher Educational Attainment ◽  
Years Of Schooling

ABSTRACTBackgroundObservational evidence suggests that higher educational attainment is protective for Alzheimer’s disease (AD). It is unclear whether this association is causal or confounded by demographic and socioeconomic characteristics. We examined the causal effect of educational attainment on AD in a two-sample MR framework.MethodsWe extracted all available effect estimates of the 74 single nucleotide polymorphisms (SNPs) associated with years of schooling from the largest genome-wide association study (GWAS) of educational attainment (N=293,723) and the GWAS of AD conducted by the International Genomics of Alzheimer’s Project (n=17,008 AD cases and 37,154 controls). SNP-exposure and SNP-outcome coefficients were combined using an inverse variance weighted approach, providing an estimate of the causal effect of each SD increase in years of schooling on AD. We also performed appropriate sensitivity analyses examining the robustness of causal effect estimates to the various assumptions and conducted simulation analyses to examine potential survival bias of MR analyses.FindingsWith each SD increase in years of schooling (3.51 years), the odds of AD were, on average, reduced by approximately one third (odds ratio= 0.63, 95% confidence interval [CI]: 0.48 to 0.83, p<0.001). Causal effect estimates were consistent when using causal methods with varying MR assumptions or different sets of SNPs for educational attainment, lending confidence to the magnitude and direction of effect in our main findings. There was also no evidence of survival bias in our study.InterpretationOur findings support a causal role of educational attainment on AD, whereby an additional ∼3.5 years of schooling reduces the odds of AD by approximately one third.

scholarly journals Mendelian randomisation analysis of the effect of educational attainment and cognitive ability on smoking behaviour

2018 ◽  
Author(s):  
Eleanor Sanderson ◽  
George Davey Smith ◽  
Jack Bowden ◽  
Marcus R. Munafò
Keyword(s):  
Educational Attainment ◽  
Health Outcomes ◽  
Cognitive Ability ◽  
Smoking Behaviour ◽  
Mendelian Randomisation ◽  
Individual Data ◽  
General Cognitive Ability ◽  
Uk Biobank ◽  
The Uk ◽  
Summary Data

AbstractRecent analyses have shown educational attainment to be associated with a number of health outcomes. This association may, in part, be due to an effect of educational attainment on smoking behaviour. In this study we apply a multivariable Mendelian randomisation design to determine whether the effect of educational attainment on smoking behaviour could be due to educational attainment or general cognitive ability. We use individual data from the UK Biobank study (N = 120,050) and summary data from large GWAS studies of educational attainment, cognitive ability and smoking behaviour. Our results show that more years of education are associated with a reduced likelihood of smoking which is not due to an effect of general cognitive ability on smoking behaviour. Given the considerable physical harms associated with smoking, the effect of educational attainment on smoking is likely to contribute to the health inequalities associated with differences in educational attainment.

scholarly journals Genetic evidence for a causative effect of airflow obstruction on left ventricular filling: a Mendelian randomisation study

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lars Harbaum ◽  
Jan K. Hennigs ◽  
Marcel Simon ◽  
Tim Oqueka ◽  
Henrik Watz ◽  
...  
Keyword(s):  
General Population ◽  
Genetic Variants ◽  
Airflow Obstruction ◽  
Left Ventricular ◽  
Sensitivity Analyses ◽  
Weighted Regression ◽  
Mendelian Randomisation ◽  
Effect Estimate ◽  
Genome Wide Association Studies ◽  
Inverse Variance

Abstract Background Observational studies on the general population have suggested that airflow obstruction associates with left ventricular (LV) filling. To limit the influence of environmental risk factors/exposures, we used a Mendelian randomisation (MR) approach based on common genetic variations and tested whether a causative relation between airflow obstruction and LV filling can be detected. Methods We used summary statistics from large genome-wide association studies (GWAS) on the ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC) measured by spirometry and the LV end-diastolic volume (LVEDV) as assessed by cardiac magnetic resonance imaging. The primary MR was based on an inverse variance weighted regression. Various complementary MR methods and subsets of the instrument variables were used to assess the plausibility of the findings. Results We obtained consistent evidence in our primary MR analysis and subsequent sensitivity analyses that reducing airflow obstruction leads to increased inflow to the LV (odds ratio [OR] from inverse variance weighted regression 1.05, 95% confidence interval [CI] 1.01–1.09, P = 0.0172). Sensitivity analyses indicated a certain extent of negative horizontal pleiotropy and the estimate from biased-corrected MR-Egger was adjusted upward (OR 1.2, 95% CI 1.09–1.31, P < 0.001). Prioritisation of single genetic variants revealed rs995758, rs2070600 and rs7733410 as major contributors to the MR result. Conclusion Our findings indicate a causal relationship between airflow obstruction and LV filling in the general population providing genetic context to observational associations. The results suggest that targeting (even subclinical) airflow obstruction can lead to direct cardiac improvements, demonstrated by an increase in LVEDV. Functional annotation of single genetic variants contributing most to the causal effect estimate could help to prioritise biological underpinnings.

scholarly journals Evidence for causal effects of lifetime smoking on risk for depression and schizophrenia: a Mendelian randomisation study

2019 ◽  
Vol 50 (14) ◽  
pp. 2435-2443 ◽  
Author(s):  
Robyn E. Wootton ◽  
Rebecca C. Richmond ◽  
Bobby G. Stuijfzand ◽  
Rebecca B. Lawn ◽  
Hannah M. Sallis ◽  
...  
Keyword(s):  
Causal Effect ◽  
Association Studies ◽  
Smoking Initiation ◽  
Smoking Behaviour ◽  
Positive Control ◽  
Mendelian Randomisation ◽  
Genome Wide Association Studies ◽  
Weak Evidence ◽  
Smoking Duration ◽  
The Uk

AbstractBackgroundSmoking prevalence is higher amongst individuals with schizophrenia and depression compared with the general population. Mendelian randomisation (MR) can examine whether this association is causal using genetic variants identified in genome-wide association studies (GWAS).MethodsWe conducted two-sample MR to explore the bi-directional effects of smoking on schizophrenia and depression. For smoking behaviour, we used (1) smoking initiation GWAS from the GSCAN consortium and (2) we conducted our own GWAS of lifetime smoking behaviour (which captures smoking duration, heaviness and cessation) in a sample of 462690 individuals from the UK Biobank. We validated this instrument using positive control outcomes (e.g. lung cancer). For schizophrenia and depression we used GWAS from the PGC consortium.ResultsThere was strong evidence to suggest smoking is a risk factor for both schizophrenia (odds ratio (OR) 2.27, 95% confidence interval (CI) 1.67–3.08, p < 0.001) and depression (OR 1.99, 95% CI 1.71–2.32, p < 0.001). Results were consistent across both lifetime smoking and smoking initiation. We found some evidence that genetic liability to depression increases smoking (β = 0.091, 95% CI 0.027–0.155, p = 0.005) but evidence was mixed for schizophrenia (β = 0.022, 95% CI 0.005–0.038, p = 0.009) with very weak evidence for an effect on smoking initiation.ConclusionsThese findings suggest that the association between smoking, schizophrenia and depression is due, at least in part, to a causal effect of smoking, providing further evidence for the detrimental consequences of smoking on mental health.

Cigarette smoking and schizophrenia: Mendelian randomisation study

2020 ◽  
pp. 1-6
Author(s):  
Jianhua Chen ◽  
Ruirui Chen ◽  
Siying Xiang ◽  
Ningning Li ◽  
Chengwen Gao ◽  
...  
Keyword(s):  
Cigarette Smoking ◽  
Association Studies ◽  
Smoking Initiation ◽  
Sensitivity Analyses ◽  
Mendelian Randomisation ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Complex Behaviour ◽  
Asian Populations ◽  
Smoking Behaviours

Background The link between schizophrenia and cigarette smoking has been well established through observational studies. However, the cause–effect relationship remains unclear. Aims We conducted Mendelian randomisation analyses to assess any causal relationship between genetic variants related to four smoking-related traits and the risk of schizophrenia. Method We performed a two-sample Mendelian randomisation using summary statistics from genome-wide association studies (GWAS) of smoking-related traits and schizophrenia (7711 cases, 18 327 controls) in East Asian populations. Single nucleotide polymorphisms (SNPs) correlated with smoking behaviours (smoking initiation, smoking cessation, age at smoking initiation and quantity of smoking) were investigated in relation to schizophrenia using the inverse-variance weighted (IVW) method. Further sensitivity analyses, including Mendelian randomisation-Egger (MR-Egger), weighted median estimates and leave-one-out analysis, were used to test the consistency of the results. Results The associated SNPs for the four smoking behaviours were not significantly associated with schizophrenia status. Pleiotropy did not inappropriately affect the results. Conclusions Cigarette smoking is a complex behaviour in people with schizophrenia. Understanding factors underlying the observed association remains important; however, our findings do not support a causal role of smoking in influencing risk of schizophrenia.

scholarly journals Causal effect of children’s secondary education on parental health outcomes: findings from a natural experiment in Botswana

BMJ Open ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. e043247
Author(s):  
Jan Ole Ludwig ◽  
Neil M Davies ◽  
Jacob Bor ◽  
Jan-Walter De Neve
Keyword(s):  
Educational Attainment ◽  
Natural Experiment ◽  
Policy Reform ◽  
Causal Effect ◽  
Sensitivity Analyses ◽  
Secondary Outcome ◽  
Secondary Schooling ◽  
Mothers And Fathers ◽  
Random Samples ◽  
Exposed Child

ObjectivesA growing literature highlights the intergenerational transmission of human capital from parents to children. However, far less is known about ‘upward transmission’ from children to parents. In this study, we use a 1996 Botswana education policy reform as a natural experiment to identify the causal effect of children’s secondary schooling on their parents’ health.SettingBotswana’s decennial census (2001 and 2011). Data were obtained through the Integrated Public Use Microdata Series and are 10% random samples of the complete population in each of these census years.ParticipantsSurvey respondents who were citizens born in Botswana, at least 18 years old at the time of the census and born in or after 1975 (n=89 721).Primary and secondary outcome measuresParental survival and disability at the time of the census, separately for mothers and fathers.ResultsThe 1996 reform caused a large increase in grade 10 enrolment, inducing an additional 0.4 years of schooling for the first cohorts affected (95% CI 0.3 to 0.5, p<0.001). The reform, however, had no effect on parental survival and disability by the time exposed child cohorts reach age 30. Results were robust to a wide array of sensitivity analyses.ConclusionsThis study found little evidence that parents’ survival and disability were affected by their offspring’s educational attainment in Botswana. Parents’ health may not be necessarily affected by increasing their offspring’s educational attainment.

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