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Educational attainment and psychiatric diagnoses: a national registry data and two-sample Mendelian randomization study

Abstract

We investigate the causal relationship between educational attainment (EA) and mental health conditions using two research designs. Here we first compare the relationship between EA and 18 psychiatric diagnoses within-sibship in Dutch national registry data (N = 1.7 million), thereby controlling for unmeasured familial factors. Second, we apply two-sample Mendelian randomization, which uses genetic variants related to EA or psychiatric diagnosis as instrumental variables, to test whether there is a causal relation in either direction. Our results suggest that lower levels of EA causally increase the risk of major depressive disorder, attention-deficit/hyperactivity disorder, alcohol dependence, generalized anxiety disorder and post-traumatic stress disorder diagnoses. We also find evidence of a causal effect of attention-deficit/hyperactivity disorder on EA. For schizophrenia, anorexia nervosa, obsessive–compulsive disorder and bipolar disorder, the results were inconsistent across the different approaches, highlighting the importance of using multiple research designs to understand complex relationships, such as between EA and mental health conditions.

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Fig. 1: Phenotypic and genetic correlations between diagnoses.
Fig. 2: Prevalence of diagnoses given someone’s EA and sex.
Fig. 3: Relation between EA and diagnoses as estimated with logistic regression, within-sibship regression or MR.
Fig. 4: MR analyses with diagnosis as exposure and EA as the outcome.
Fig. 5: Average number of years of education of patients, healthy siblings of patients and unaffected sibships.

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Data availability

We analyze restricted access microdata from Statistics Netherlands (CBS), accessed under the project 8590. All microdata used in this project are reported in Methods and Supplementary Note 1. Under strict conditions, these microdata are accessible for statistical and scientific research. Further information on remote access procedures can be found via microdata@cbs.nl. For GWAS summary statistics availability, see original publications. For 23andMe, Inc. dataset access, see https://research.23andme.com/dataset-access/ (ref. 78).

Code availability

All code associated with the analyses is available on GitHub at https://github.com/PerlineDemange/CBS-MR (ref. 63).

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Acknowledgements

We thank the Open Data Infrastructure for Social Science and Economic Innovation (ODISSEI: https://ror.org/03m8v6t10) for financing access to Statistics Netherlands microdata via a microdata access grant awarded to P.A.D. and a member discount. P.A.D. is supported by the grant 531003014 from The Netherlands Organisation for Health Research and Development (ZonMW) and by the European Union (Grant agreement No. 101045526). Views and opinions expressed are, however, those of the authors only and do not necessarily reflect those of the European Union or the European Research Council Executive Agency. Neither the European Union nor the granting authority can be held responsible for them. D.I.B. is supported by the Royal Netherlands Academy of Science Professor Award (PAH/6635). E.v.B. is supported by ZonMW grant 531003014 and VENI grant 451-15-017. M.G.N. is supported by R01MH120219, ZonMW grants 849200011 and 531003014 from the Netherlands Organisation for Health Research and Development and a VENI grant awarded by the Dutch Research Council (NWO; VI.Veni.191G.030) and is a Jacobs Foundation Research Fellow. We thank the research participants and employees of 23andMe, Inc. for making this work possible.

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P.A.D. and M.G.N. conceived and designed the study, with helpful suggestions from E.v.B. and D.I.B. P.A.D. analyzed the data, with support from M.G.N. for the MR analyses. P.A.D. designed the figures and drafted the paper. All authors contributed to and approved the final version of the paper.

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Correspondence to Perline A. Demange.

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Demange, P.A., Boomsma, D.I., van Bergen, E. et al. Educational attainment and psychiatric diagnoses: a national registry data and two-sample Mendelian randomization study. Nat. Mental Health 2, 668–679 (2024). https://doi.org/10.1038/s44220-024-00245-x

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