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Instrumental variable approaches to identifying the causal effect of educational attainment on dementia risk.

ABSTRACT: Education is an established correlate of cognitive status in older adulthood, but whether expanding educational opportunities would improve cognitive functioning remains unclear given limitations of prior studies for causal inference. Therefore, we conducted instrumental variable (IV) analyses of the association between education and dementia risk, using for the first time in this area, genetic variants as instruments as well as state-level school policies.IV analyses in the Health and Retirement Study cohort (1998-2010) used two sets of instruments: (1) a genetic risk score constructed from three single-nucleotide polymorphisms (SNPs; n = 7981); and (2) compulsory schooling laws (CSLs) and state school characteristics (term length, student teacher ratios, and expenditures; n = 10,955).Using the genetic risk score as an IV, there was a 1.1% reduction in dementia risk per year of schooling (95% confidence interval, -2.4 to 0.02). Leveraging compulsory schooling laws and state school characteristics as IVs, there was a substantially larger protective effect (-9.5%; 95% confidence interval, -14.8 to -4.2). Analyses evaluating the plausibility of the IV assumptions indicated estimates derived from analyses relying on CSLs provide the best estimates of the causal effect of education.IV analyses suggest education is protective against risk of dementia in older adulthood.

SUBMITTER: Nguyen TT

PROVIDER: S-EPMC4688127 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Instrumental variable approaches to identifying the causal effect of educational attainment on dementia risk.

Nguyen Thu T TT Tchetgen Tchetgen Eric J EJ Kawachi Ichiro I Gilman Stephen E SE Walter Stefan S Liu Sze Y SY Manly Jennifer J JJ Glymour M Maria MM

Annals of epidemiology 20151030 1

<h4>Purpose</h4>Education is an established correlate of cognitive status in older adulthood, but whether expanding educational opportunities would improve cognitive functioning remains unclear given limitations of prior studies for causal inference. Therefore, we conducted instrumental variable (IV) analyses of the association between education and dementia risk, using for the first time in this area, genetic variants as instruments as well as state-level school policies.<h4>Methods</h4>IV anal ...[more]

PMID: 26633592

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Project description:Vitamin D deficiency has been associated with several common diseases, including cancer and is being investigated as a possible risk factor for these conditions. We reported the striking prevalence of vitamin D deficiency in Scotland. Previous epidemiological studies have reported an association between low dietary vitamin D and colorectal cancer (CRC). Using a case-control study design, we tested the association between plasma 25-hydroxy-vitamin D (25-OHD) and CRC (2,001 cases, 2,237 controls). To determine whether plasma 25-OHD levels are causally linked to CRC risk, we applied the control function instrumental variable (IV) method of the mendelian randomization (MR) approach using four single nucleotide polymorphisms (rs2282679, rs12785878, rs10741657, rs6013897) previously shown to be associated with plasma 25-OHD. Low plasma 25-OHD levels were associated with CRC risk in the crude model (odds ratio (OR): 0.76, 95% Confidence Interval (CI): 0.71, 0.81, p: 1.4×10(-14)) and after adjusting for age, sex and other confounding factors. Using an allele score that combined all four SNPs as the IV, the estimated causal effect was OR 1.16 (95% CI 0.60, 2.23), whilst it was 0.94 (95% CI 0.46, 1.91) and 0.93 (0.53, 1.63) when using an upstream (rs12785878, rs10741657) and a downstream allele score (rs2282679, rs6013897), respectively. 25-OHD levels were inversely associated with CRC risk, in agreement with recent meta-analyses. The fact that this finding was not replicated when the MR approach was employed might be due to weak instruments, giving low power to demonstrate an effect (<0.35). The prevalence and degree of vitamin D deficiency amongst individuals living in northerly latitudes is of considerable importance because of its relationship to disease. To elucidate the effect of vitamin D on CRC cancer risk, additional large studies of vitamin D and CRC risk are required and/or the application of alternative methods that are less sensitive to weak instrument restrictions.

Project description:BackgroundThere is ongoing debate about whether education or socioeconomic status (SES) should be inputs into cardiovascular disease (CVD) prediction algorithms and clinical risk adjustment models. It is also unclear whether intervening on education will affect CVD, in part because there is controversy regarding whether education is a determinant of CVD or merely correlated due to confounding or reverse causation. We took advantage of a natural experiment to estimate the population-level effects of educational attainment on CVD and related risk factors.Methods and findingsWe took advantage of variation in United States state-level compulsory schooling laws (CSLs), a natural experiment that was associated with geographic and temporal differences in the minimum number of years that children were required to attend school. We linked census data on educational attainment (N = approximately 5.4 million) during childhood with outcomes in adulthood, using cohort data from the 1992-2012 waves of the Health and Retirement Study (HRS; N = 30,853) and serial cross-sectional data from 1971-2012 waves of the National Health and Nutrition Examination Survey (NHANES; N = 44,732). We examined self-reported CVD outcomes and related risk factors, as well as relevant serum biomarkers. Using instrumental variables (IV) analysis, we found that increased educational attainment was associated with reduced smoking (HRS β -0.036, 95%CI: -0.06, -0.02, p < 0.01; NHANES β -0.032, 95%CI: -0.05, -0.02, p < 0.01), depression (HRS β -0.049, 95%CI: -0.07, -0.03, p < 0.01), triglycerides (NHANES β -0.039, 95%CI: -0.06, -0.01, p < 0.01), and heart disease (HRS β -0.025, 95%CI: -0.04, -0.002, p = 0.01), and improvements in high-density lipoprotein (HDL) cholesterol (HRS β 1.50, 95%CI: 0.34, 2.49, p < 0.01; NHANES β 0.86, 95%CI: 0.32, 1.48, p < 0.01), but increased BMI (HRS β 0.20, 95%CI: 0.002, 0.40, p = 0.05; NHANES β 0.13, 95%CI: 0.01, 0.32, p = 0.05) and total cholesterol (HRS β 2.73, 95%CI: 0.09, 4.97, p = 0.03). While most findings were cross-validated across both data sets, they were not robust to the inclusion of state fixed effects. Limitations included residual confounding, use of self-reported outcomes for some analyses, and possibly limited generalizability to more recent cohorts.ConclusionsThis study provides rigorous population-level estimates of the association of educational attainment with CVD. These findings may guide future implementation of interventions to address the social determinants of CVD and strengthen the argument for including educational attainment in prediction algorithms and primary prevention guidelines for CVD.

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Instrumental variable approaches to identifying the causal effect of educational attainment on dementia risk.

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Instrumental variable approaches to identifying the causal effect of educational attainment on dementia risk.

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