The role of literacy in the association between educational attainment and depressive symptoms

There is a consistent association between education and depressive symptoms, but research on the mechanisms to explain this association remains limited. No study has formally evaluated the extent to which the association between education and depressive symptoms is mediated through a foundational skill such as literacy. Inverse odds ratio weighting (IORW) was used to estimate total, natural direct, and natural indirect effects in examining literacy as a mediator of the association between education and depressive symptoms. Health and Retirement Study participants born in the U.S. between 1900 and 1947 were interviewed biennially for up to 12 years (N = 16,718). Literacy was assessed with a brief vocabulary measure. Depressive symptoms were measured using the 8-item Centers for Epidemiologic Studies-Depression (CES-D) scale. Decomposition estimates were derived using regression analyses of repeated measures of depressive symptoms. Standard errors were obtained using a nonparametric bootstrap with the individual as the independent unit to account for dependence of observations within an individual. In a large cohort of older Americans, a one standard deviation difference in educational attainment (~ 3 years) was associated with a 0.35-point decrement in CES-D score (95% CI: -0.38, -0.32). This decrement represents a 0.22 standard deviation difference in depressive symptoms. Using IORW, the estimated effect of education on depressive symptoms mediated through literacy was -0.10 (95% CI: -0.18, -0.01), which represents 28% of the total effect. Education confers many benefits; as demonstrated by this study for depressive symptoms, one important benefit is literacy

Integrated multiple mediation analysis: A robustness–specificity trade-off in causal structure

Recent methodological developments in causal mediation analysis have addressed several issues regarding multiple mediators. However, these developed methods differ in their definitions of causal parameters, assumptions for identification, and interpretations of causal effects, making it unclear which method ought to be selected when investigating a given causal effect. Thus, in this study, we construct an integrated framework, which unifies all existing methodologies, as a standard for mediation analysis with multiple mediators. To clarify the relationship between existing methods, we propose four strategies for effect decomposition: two-way, partially forward, partially backward, and complete decompositions. This study reveals how the direct and indirect effects of each strategy are explicitly and correctly interpreted as path-specific effects under different causal mediation structures. In the integrated framework, we further verify the utility of the interventional analogues of direct and indirect effects, especially when natural direct and indirect effects cannot be identified or when cross-world exchangeability is invalid. Consequently, this study yields a robustness–specificity trade-off in the choice of strategies. Inverse probability weighting is considered for estimation. The four strategies are further applied to a simulation study for performance evaluation and for analyzing the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer data set from Taiwan to investigate the causal effect of hepatitis C virus infection on mortality

An IPW estimator for mediation effects in hazard models: with an application to schooling, cognitive ability and mortality

Large differences in mortality rates across those with different levels of education are a well-established fact. Cognitive ability may be affected by education so that it becomes a mediating factor in the causal chain. In this paper, we estimate the impact of education on mortality using inverse-probability-weighted (IPW) estimators. We develop an IPW estimator to analyse the mediating effect in the context of survival models. Our estimates are based on administrative data, on men born between 1944 and 1947 who were examined for military service in the Netherlands between 1961 and 1965, linked to national death records. For these men, we distinguish four education levels and we make pairwise comparisons. The results show that levels of education have hardly any impact on the mortality rate. Using the mediation method, we only find a significant effect of education on mortality running through cognitive ability, for the lowest education group that amounts to a 15% reduction in the mortality rate. For the highest education group, we find a significant effect of education on mortality through other pathways of 12%

Validation of a polygenic risk score for dementia in black and white individuals

OBJECTIVE: To determine whether a polygenic risk score for Alzheimer's disease (AD) predicts dementia probability and memory functioning in non-Hispanic black (NHB) and non-Hispanic white (NHW) participants from a sample not used in previous genome-wide association studies. METHODS: Non-Hispanic white and NHB Health and Retirement Study (HRS) participants provided genetic information and either a composite memory score (n = 10,401) or a dementia probability score (n = 7690). Dementia probability score was estimated for participants' age 65+ from 2006 to 2010, while memory score was available for participants age 50+. We calculated AD genetic risk scores (AD-GRS) based on 10 polymorphisms confirmed to predict AD, weighting alleles by beta coefficients reported in AlzGene meta-analyses. We used pooled logistic regression to estimate the association of the AD-GRS with dementia probability and generalized linear models to estimate its effect on memory score. RESULTS: Each 0.10 unit change in the AD-GRS was associated with larger relative effects on dementia among NHW aged 65+ (OR = 2.22; 95% CI: 1.79, 2.74; P < 0.001) than NHB (OR=1.33; 95% CI: 1.00, 1.77; P = 0.047), although additive effect estimates were similar. Each 0.10 unit change in the AD-GRS was associated with a −0.07 (95% CI: −0.09, −0.05; P < 0.001) SD difference in memory score among NHW aged 50+, but no significant differences among NHB (β = −0.01; 95% CI: −0.04, 0.01; P = 0.546). [Correction added on 29 July 2014, after first online publication: confidence intervalshave been amended.] The estimated effect of the GRS was significantly smaller among NHB than NHW (P < 0.05) for both outcomes. CONCLUSION: This analysis provides evidence for differential relative effects of the GRS on dementia probability and memory score among NHW and NHB in a new, national data set

Genome-wide polygenic scoring for a 14-year long-term average depression phenotype

Background: Despite moderate heritability estimates for depression-related phenotypes, few robust genetic predictors have been identified. Potential explanations for this discrepancy include the use of phenotypic measures taken from a single time point, r