School performance and genetic propensities for educational attainment and depression in the etiology of self-harm: a Danish population-based study

Abstract

Background

Poor school performance is linked to higher risks of self-harm. The association might be explained through genetic liabilities for depression or educational attainment. We investigated the association between school performance and self-harm in a population-based sample while assessing the potential influence of polygenic risk scores (PRSs) for depression (PRS_MDD) and for educational attainment (PRS_EDU).

Method

We conducted a follow-up study of individuals born 1987–98 and followed from age 18 until 2016. The total sample consisted of a case group (23,779 diagnosed with mental disorders; schizophrenia, bipolar disorder, depression, autism, and attention deficit hyperactivity disorder (ADHD) and a randomly sampled comparison group (n = 10,925). Genome-wide data were obtained from the Neonatal Screening Biobank and information on school performance, family psychiatric history, and socioeconomic status from national administrative registers.

Results

Individuals in the top PRS_MDD decile were at higher self-harm risk in the case group (IRR: 1.30; 95% CI 1.15–1.46), whereas individuals in the top PRS_EDU decile were at lower self-harm risk (IRR: 0.63; 95% CI: 0.55–0.74). Poorer school performance was associated with higher self-harm risk in persons diagnosed with any mental disorder (IRR: 1.69; 95% CI: 1.44–1.99) and among the comparison group (IRR: 7.93; 95% CI: 4.47–15.18). Observed effects of PRS_MDD and PRS_EDU on self-harm risk were strongest for individuals with poor school performance.

Conclusion

Associations between PRS_MDD and self-harm risk and between PRS_EDU and self-harm risk were found. Nevertheless, these polygenic scores seem currently of limited clinical utility for identifying individuals at high self-harm risk.

Keywords:

• School-performance
• self-harm
• mental disorders
• polygenic risk scores
• linkage data

Disclosure statement

The authors declare no financial interests or potential conflicts of interest.

Data availability statement

Due to safety regulations, data are not available to share.

Additional information

Funding

Genotyping of the iPSYCH2012 samples was supported by grant numbers R102-A9118 and R155-2014-1724 from the Lundbeck Foundation, the Stanley Foundation, the Simons Foundation (SFARI 311789), and the National Institutes of Mental Health (NIMH 5U01MH094432-02). The Danish National Biobank resource is supported by the Novo Nordisk Foundation. The authors gratefully acknowledge the Psychiatric Genomics Consortium (PGC), the Social Science Genetic Association Consortium (SSGAC) and the research participants and employees of 23andMe, Inc. for providing the summary statistics used to general the polygenic risk scores.

Notes on contributors

Holger J. Sørensen

Associate professor Holger J. Sørensen is chief physician at Mental Health Centre Copenhagen. He has a H-index of 32. His scientific focus is epidemiology, alcohol use disorder, high-risk studies and premorbid cognitive function in relation to mental disorder.

Sussie Antonsen

Sussie Antonsen, MSc, is a research assistant at the National Centre for Register-based Research, Aarhus University, Denmark. She has more than 14 years of experience in working with data management and statistical analyses of the Danish national health registers.

Michael E. Benros

Prof. Michael E. Benros, MD, PhD, is chief physician and professor at Mental Health Centre Copenhagen and the University of Copenhagen. He is among the Clarivate highly cited researchers and board member of several international organizations (Orcid ID: 0000-0003-4939-9465). His scientific focus is epidemiology, immunopsychiatry, genetics, and precision psychiatry.

Annette Erlangsen

Annette Erlangsen PhD is Head of Program at Danish Research Institute for Suicide Prevention, Mental Health Centre Copenhagen. She is affiliated to Johns Hopkins School of Public Health, USA and Australian National University. Her expertise is population-based and intervention studies with a focus on suicide prevention (Orcid ID: 0000-0003-3475-0558).

Clara Albiñana

Clara Albiñana, MSc, BSc is a PhD student in Statistical Genetics at the graduate school of Health at Aarhus University, Denmark. Clara is supervised by Bjarni J. Vilhjalmsson and has over 10 peer-review publications in the use of polygenic risk scores in epidemiology and genetics of mental disorders.

Merete Nordentoft

Merete Nordentoft is a clinical psychiatrist and Professor of Psychiatry, University of Copenhagen. She is an expert in epidemiology, suicidal behaviour, psychopathology and early intervention in psychosis. She has worked with suicide prevention at a national level since 1997, and she is involved in unravelling excess mortality in mental illness.

Anders D. Børglum

Anders Børglum is Professor of Medical Genetics and Chair of Personalized Medicine Research at Department of Biomedicine, Aarhus University. His research focuses on identifying genes that confer risk or resilience to psychiatric disorders, functional characterization of the identified genes and translating the genetic insights to advance precision medicine in psychiatry.

Ole Mors

Ole Mors is a Professor in the Psychosis Research Unit, Department of Clinical Medicine, University of Aarhus, Denmark. His research focuses on identifying genetic and environmental risk factors for mental disorders. Our unit consists of psychiatrists, nurses, psychologists, molecular biologists and statisticians, totalling twenty researchers, including a professor, a consultant, four associate professors, four postdocs, seven PhD students and three research assistants.

Thomas Werge

Thomas Werge is the director of Institute of Biological Psychiatry (Copenhagen University Hospital), and professor of psychiatry (University of Copenhagen). He is an expert in psychiatric and complex traits genetic and epidemiology, a founder of numerous international disease genomics initiatives and leading translational efforts in clinical psychiatry.

Preben B. Mortensen

Preben Bo Mortensen is a Professor and Head of the National Center for Register-Based Research at Aarhus University, Denmark. He is an expert in psychiatric epidemiology, suicidology, psychiatric genetics, and related socioeconomic and demographic components. He has conducted research in psychiatric epidemiology and psychiatric genetics for more than 35 years.

David Hougaard

David M. Hougaard, MD, DMSC is Head of Danish Center for Neonatal Screening and Director Department for Congenital Disorders at Statens Serum Institute, Denmark. He has scientifically collaborated with several institutions in USA and Europe with focus on neonatal screening and cell biology as well as genetic, epigenetic and biomarker connections to metabolic, endocrine, psychiatric and cancer disorders.

Roger T. Webb

Roger Webb joined the University of Manchester during 1998, where he received his PhD in Epidemiology in 2002. He is currently Professor of Mental Health Epidemiology. He conducts population-based studies of adverse outcomes in people diagnosed with mental illnesses, with a particular interest in investigating the determinants of non-fatal self-harm and suicide.

Esben Agerbo

Professor Esben Agerbo, DrMedSc, MSc, BSc is employed at the National Centre for Register-based Research, Aarhus University, Denmark. Dr Agerbo (H-index 62) has published more than 270 peer-reviewed publications (http://orcid.org/0000-0002-2849-524X) that cited over 20,000 times. Dr Agerbo’s scientific focus is the epidemiology and genetics of mental disorders and suicidal behaviour.