Biology subjects

Vaucher, J.

Publications and source records attributed to Vaucher, J..

3 recordsLinked to original sources

bioRxiv2018

What explains the effect of education on cardiovascular disease? Applying Mendelian randomization to identify the consequences of education inequality

Key PointsO_ST_ABSQuestionC_ST_ABSWhat is the role of body mass index, systolic blood pressure and smoking in mediating the effect of education on cardiovascular disease risk?\n\nFindingWe find consistent evidence that body mass index, systolic blood pressure and smoking mediate the effect of education, explaining up to 18%, 27% and 33% respectively. Including all three risk factors in a model together explains around 40% of the effect of education.\n\nMeaningIntervening on body mass index, systolic blood pressure and smoking would lead to reductions in cases of CVD attributable to lower levels of education. Over half of the effect of education on risk of cardiovascular disease is not mediated through these risk factors.\n\nImportanceLower levels of education are causally related to higher cardiovascular risk, but the extent to which this is driven by modifiable risk factors also associated with education is unknown.\n\nObjectiveTo investigate the role of body mass index, systolic blood pressure and smoking in explaining the effect of education on risk of cardiovascular disease outcomes.\n\nDesignMultivariable regression analysis of observational data and Mendelian randomization (MR) analysis of genetic data.\n\nSettingUK Biobank and international genome-wide association study consortia.\n\nParticipantsPredominantly individuals of European ancestry.\n\nMain outcomes and measuresThe effects of education (per 1-standard deviation increase, equivalent to 3.6 years) on coronary heart disease, cardiovascular disease (all subtypes), myocardial infarction and stroke risk (all measured in odds ratio, OR), and the degree to which this is mediated through body mass index, systolic blood pressure and smoking.\n\nResultsEach additional standard deviation of education associated with 13% lower risk of coronary heart disease (OR 0.87, 95% confidence interval [CI] 0.84 to 0.89) in observational analysis and 37% lower risk (OR 0.63, 95% CI 0.60 to 0.67) in Mendelian randomization analysis. As a proportion of the total risk reduction, body mass index mediated 15% (95% CI 13% to 17%) and 18% (95% CI 14% to 23%) in the observational and Mendelian randomization estimates, respectively. Corresponding estimates for systolic blood pressure were 11% (95% CI 9% to 13%) and 21% (95% CI 15% to 27%), and for smoking, 19% (15% to 22%) and 33% (95% CI 17% to 49%). All three risk factors combined mediated 42% (95% CI 36% to 48%) and 36% (95 % CI 16% to 63%) of the effect of education on coronary heart disease in observational and Mendelian randomization respectively. Similar results were obtained when investigating risk of stroke, myocardial infarction and all-cause cardiovascular disease.\n\nConclusions and relevanceBMI, SBP and smoking mediate a substantial proportion of the protective effect of education on risk of cardiovascular outcomes and intervening on these would lead to reductions in cases of CVD attributable to lower levels of education. However, more than half of the protective effect of education remains unexplained and requires further investigation.

epidemiology↗

bioRxiv2017

Education and coronary heart disease: a Mendelian randomization study

ObjectivesTo determine whether educational attainment is a causal risk factor in the development of coronary heart disease.\n\nDesignMendelian randomization study, where genetic data are used as proxies for education, in order to minimize confounding. A two-sample design was applied, where summary level genetic data was analysed from two publically available consortia.\n\nSettingIn the main analysis, we analysed genetic data from two large consortia (CARDIoGRAM and SSGAC), comprising of 112 cohorts from predominantly high-income countries. In addition, we also analysed genetic data from 7 additional large consortia, in order to identify putative causal mediators.\n\nParticipantsThe main analysis was of 589 377 men and women, predominantly of European origin.\n\nExposureA one standard deviation increase in the genetic predisposition towards higher education (i.e. 3.6 years of additional schooling). This was measured by 162 genetic variants that have been previously associated with education.\n\nMain outcomeCombined fatal and nonfatal coronary heart disease (63 746 events).\n\nResults3.6 years of additional education lowered the risk of coronary heart disease by a third (odds ratio = 0.67, 95% confidence interval [CI], 0.59 to 0.77, p=0.01). Equivalent increases in education were also causally associated with reductions in smoking, BMI and improvements in blood lipid profiles.\n\nConclusionsMore time spent in education is causally associated with a large reduction in the risk of coronary heart disease. This may be partly explained by changes to smoking, BMI and a blood lipids. These findings offer support for policy interventions that increase education, in order to also reduce the burden of cardiovascular disease.

epidemiology↗

bioRxiv2016

Cannabis use and risk of schizophrenia:a Mendelian randomization study

Cannabis use is observationally associated with an increased risk of schizophrenia, however whether the relationship is causal is not known. To determine the nature of the association between cannabis use on risk of schizophrenia using Mendelian randomization (MR) analysis, we used ten genetic variants previously identified to associate with cannabis use in 32,330 individuals. Genetic variants were used in a MR analyses of the association of genetically determined cannabis on risk of schizophrenia in 34,241 cases and 45,604 controls from predominantly European descent. Estimates from MR were compared to a metaanalysis of observational studies reporting effect estimates for ever use of cannabis and risk of schizophrenia or related disorders. Genetically determined use of cannabis was associated with increased risk of schizophrenia (OR of schizophrenia for users vs. non-users of cannabis: 1.37; 95%CI, 1.09 to 1.67; P-value=0.007). The corresponding estimate from observational analysis was 1.50 (95% CI, 1.10 to 2.00; P-value for heterogeneity = 0.88). The genetic instrument did not show evidence of pleiotropy on MR-Egger (Egger test, P-value=0.292) nor on multivariable MR accounting for tobacco exposure (OR of schizophrenia for users vs. nonusers of cannabis, adjusted for ever vs. never smoker: 1.41; 95% CI, 1.09-1.83). Furthermore, the causal estimate remained robust to sensitivity analyses. These findings strongly support a causal association between genetically determined use of cannabis and risk of schizophrenia. Such robust evidence may inform public health message about the risks of cannabis use, especially regarding its potential mental health consequences.

epidemiology↗