TY - JOUR
T1 - Understanding the consequences of education inequality on cardiovascular disease
T2 - Mendelian randomisation study
AU - Carter, Alice R.
AU - Gill, Dipender
AU - Davies, Neil M.
AU - Taylor, Amy E.
AU - Tillmann, Taavi
AU - Vaucher, Julien
AU - Wootton, Robyn E.
AU - Munafò, Marcus R.
AU - Hemani, Gibran
AU - Malik, Rainer
AU - Seshadri, Sudha
AU - Woo, Daniel
AU - Burgess, Stephen
AU - Davey Smith, George
AU - Holmes, Michael V.
AU - Tzoulaki, Ioanna
AU - Howe, Laura D.
AU - Dehghan, Abbas
N1 - Funding Information:
(FS/18/23/33512) and the National Institute for Health Research Oxford Biomedical Research Centre. LDH is funded by a Career Development Award from the UK Medical Research Council (MR/ M020894/1). Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf. ARC, DG, TT, JV, REW, GH, RM, SS, SB, GDS, MVH, IT, and AD declare no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. MRM reports grants from Pfizer and non-financial support from GlaxoSmithKline, outside the submitted work. NMD reports grants from ESRC, grants from MRC, during the conduct of the study; grants from GRAND/Pfizer for unrelated research, outside the submitted work. AET reports grants from Pfizer, outside the submitted work. LDH reports grants from MRC, during the conduct of the study. DW reports grants from NIH, during the conduct of the study.
Funding Information:
Funding: No funding body has influenced data collection, analysis or its interpretations. This work was carried out using the computational facilities of the Advanced Computing Research Centre and the Research Data Storage Facility of the University of Bristol. This research was conducted using the UK Biobank Resource using application 10953. ARC is funded by an MRC PhD stipend at the MRC IEU, University of Bristol (MC_UU_00011/1). ARC, NMD, REW, MRM, GH, GDS, and LDH work in a unit that receives core funding from the MRC and University of Bristol (MC_UU_00011/1/ MC_UU_00011/7). DG is funded by the Wellcome 4i Clinical PhD Programme at Imperial College London. The Economics and Social Research Council (ESRC) support NMD via a Future Research Leaders grant (ES/N000757/1). AET, REW, MRM and GDS are supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at University Hospitals Bristol NHS Foundation and the University of Bristol. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. TT is funded by an NIHR Academic Clinical Lectureship. This work was supported by the National Heart, Lung, and Blood Institute’s Framingham Heart Study (contracts N01-HC-25195 and HHSN268201500001I) and by grants from the National Institute on Ageing: R01AG033193, U01AG049505, U01AG058589, U01AG52409, R01AG054076 (SS). SS was also supported by additional grants from the National Institute on Ageing (R01AG049607, R01AG033040, RFAG1059421, RF1AG061872) and the National Institute of Neurological Disorders and Stroke (R01-NS017950, NS100605). The content is solely the responsibility of the authors and does not necessarily represent the official views of the US National Institutes of Health. DW acknowledges NIH Funding (NS036695 and NS030678). MVH works in a unit that receives funding from the UK Medical Research Council and is supported by a British Heart Foundation Intermediate Clinical Research Fellowship
Publisher Copyright:
© 2019 BMJ Publishing Group Limited. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2019
Y1 - 2019
N2 - Objectives To investigate the role of body mass index (BMI), systolic blood pressure, and smoking behaviour in explaining the effect of education on the risk of cardiovascular disease outcomes. Design Mendelian randomisation study. Setting UK Biobank and international genome-wide association study data. Participants Predominantly participants of European ancestry. Exposure Educational attainment, BMI, systolic blood pressure, and smoking behaviour in observational analysis, and randomly allocated genetic variants to instrument these traits in mendelian randomisation. Main outcomes measure The risk of coronary heart disease, stroke, myocardial infarction, and cardiovascular disease (all subtypes; all measured in odds ratio), and the degree to which this is mediated through BMI, systolic blood pressure, and smoking behaviour respectively. Results Each additional standard deviation of education (3.6 years) was associated with a 13% lower risk of coronary heart disease (odds ratio 0.86, 95% confidence interval 0.84 to 0.89) in observational analysis and a 37% lower risk (0.63, 0.60 to 0.67) in mendelian randomisation analysis. As a proportion of the total risk reduction, BMI was estimated to mediate 15% (95% confidence interval 13% to 17%) and 18% (14% to 23%) in the observational and mendelian randomisation estimates, respectively. Corresponding estimates were 11% (9% to 13%) and 21% (15% to 27%) for systolic blood pressure and 19% (15% to 22%) and 34% (17% to 50%) for smoking behaviour. All three risk factors combined were estimated to mediate 42% (36% to 48%) and 36% (5% to 68%) of the effect of education on coronary heart disease in observational and mendelian randomisation analyses, respectively. Similar results were obtained when investigating the risk of stroke, myocardial infarction, and cardiovascular disease. Conclusions BMI, systolic blood pressure, and smoking behaviour mediate a substantial proportion of the protective effect of education on the risk of cardiovascular outcomes and intervening on these would lead to reductions in cases of cardiovascular disease attributable to lower levels of education. However, more than half of the protective effect of education remains unexplained and requires further investigation.
AB - Objectives To investigate the role of body mass index (BMI), systolic blood pressure, and smoking behaviour in explaining the effect of education on the risk of cardiovascular disease outcomes. Design Mendelian randomisation study. Setting UK Biobank and international genome-wide association study data. Participants Predominantly participants of European ancestry. Exposure Educational attainment, BMI, systolic blood pressure, and smoking behaviour in observational analysis, and randomly allocated genetic variants to instrument these traits in mendelian randomisation. Main outcomes measure The risk of coronary heart disease, stroke, myocardial infarction, and cardiovascular disease (all subtypes; all measured in odds ratio), and the degree to which this is mediated through BMI, systolic blood pressure, and smoking behaviour respectively. Results Each additional standard deviation of education (3.6 years) was associated with a 13% lower risk of coronary heart disease (odds ratio 0.86, 95% confidence interval 0.84 to 0.89) in observational analysis and a 37% lower risk (0.63, 0.60 to 0.67) in mendelian randomisation analysis. As a proportion of the total risk reduction, BMI was estimated to mediate 15% (95% confidence interval 13% to 17%) and 18% (14% to 23%) in the observational and mendelian randomisation estimates, respectively. Corresponding estimates were 11% (9% to 13%) and 21% (15% to 27%) for systolic blood pressure and 19% (15% to 22%) and 34% (17% to 50%) for smoking behaviour. All three risk factors combined were estimated to mediate 42% (36% to 48%) and 36% (5% to 68%) of the effect of education on coronary heart disease in observational and mendelian randomisation analyses, respectively. Similar results were obtained when investigating the risk of stroke, myocardial infarction, and cardiovascular disease. Conclusions BMI, systolic blood pressure, and smoking behaviour mediate a substantial proportion of the protective effect of education on the risk of cardiovascular outcomes and intervening on these would lead to reductions in cases of cardiovascular disease attributable to lower levels of education. However, more than half of the protective effect of education remains unexplained and requires further investigation.
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U2 - 10.1136/bmj.l1855
DO - 10.1136/bmj.l1855
M3 - Article
C2 - 31122926
AN - SCOPUS:85066035290
SN - 0959-8146
VL - 365
JO - The BMJ
JF - The BMJ
M1 - l1855
ER -