Educational attainment and mental health conditions: a within-sibship Mendelian randomization study

Abstract

Importance: Observational studies have demonstrated consistent protective effects of higher educational attainment (EA) on the risk of suffering mental health conditions (MHC). Determining whether these beneficial effects are causal is challenging given the potential role of dynastic effects and demographic factors (assortative mating and population structure) in this association.

Objective: To evaluate to what extent the relationship between EA and various MHC is independent from dynastic effects and demographic factors.

Design: Within-sibship Mendelian randomization (MR) study.

Setting: One-sample MR analyses included participants' data from the Trøndelag Health Study (HUNT, Norway) and UK Biobank (United Kingdom). For two-sample MR analyses we used summary statistics from publicly available genome-wide-association-studies.

Participants: 61 880 siblings (27 507 sibships).

Exposure: Years of education.

Main outcomes: Scores for symptoms of anxiety, depression and neuroticism using the Hospital Anxiety Depression Scale (HADS), the 7-item Generalized Anxiety Disorder Scale (GAD-7), the 9-item Patient Health Questionnaire (PHQ-9), and the Eysenck Personality Questionnaire, as well as self-reported consumption of psychotropic medication.

Results: One standard deviation (SD) unit increase in years of education was associated with a lower symptom score of anxiety (-0.20 SD [95%CI: -0.26, -0.14]), depression (-0.11 SD [-0.43, 0.22]), neuroticism (-0.30 SD [-0.53, -0.06]), and lower odds of psychotropic medication consumption (OR: 0.60 [0.52, 0.69]). Estimates from the within-sibship MR analyses showed some attenuation, which however were suggestive of a causal association (anxiety: -0.17 SD [-0.33, -0.00]; depression: -0.18 SD [-1.26, 0.89]; neuroticism: -0.29 SD [-0.43, -0.15]); psychotropic medication consumption: OR, 0.52 [0.34, 0.82]).

Conclusions and relevance: Associations between EA and MHC in adulthood, although to some extend explained by dynastic effects and demographic factors, overall remain robust, indicative of a causal effect. However, larger studies are warranted to improve statistical power and further validate our conclusions.

Keywords: Mendelian randomization; anxiety; depression; educational attainment; neuroticism; psychotropic medication.

Figure 1.. Educational attainment and symptoms of anxiety.

Standard deviation (SD) changes in the anxiety score and its 95% confidence interval per SD increase in years of education are shown. Estimated associations are displayed for ordinary least square regression (OLS) and Mendelian randomization models. Abbreviations: SD, standard deviation unit; OLS EA, ordinary least square regression model with educational attainment as exposure; OLS PGS-edu, ordinary least square regression model with the educational attainment polygenic score as exposure; 1SMR, one-sample Mendelian randomization.

Figure 2.. Educational attainment and symptoms of depression.

Standard deviation (SD) changes in the depression score and its 95% confidence interval per SD increase in years of education are shown. Estimated associations are displayed for ordinary least square regression (OLS) and Mendelian randomization models. Abbreviations: SD, standard deviation unit; OLS EA, ordinary least square regression model with educational attainment as exposure; OLS PGS-edu, ordinary least square regression model with the educational attainment polygenic score as exposure; 1SMR, one-sample Mendelian randomization; 2SMR, two-sample Mendelian randomization.

Figure 3.. Educational attainment and neuroticism.

Standard deviation (SD) changes in the neuroticism score and its 95% confidence interval per SD increase in years of education are shown. Estimated associations are displayed for ordinary least square regression (OLS) and Mendelian randomization models. Abbreviations: SD, standard deviation unit; OLS EA, ordinary least square regression model with educational attainment as exposure; OLS PGS-edu, ordinary least square regression model with the educational attainment polygenic score as exposure; 1SMR, one-sample Mendelian randomization; 2SMR, two-sample Mendelian randomization.

Figure 4.. Educational attainment and consumption of psychotropic medication.

Log odds changes in consumption of psychotropic medication and its 95% confidence interval per SD increase in years of education are shown. Estimated associations are displayed for logistic regression (LOG) and Mendelian randomization models. Abbreviations: SD, standard deviation unit; LOG EA, logistic regression model with educational attainment as exposure; LOG PGS-edu, logistic regression model with the educational attainment polygenic score as exposure; 1SMR, one-sample Mendelian randomization.