Polygenic Risk of Mental Disorders and Subject-Specific School Grades

Oskar Hougaard Jefsen; Katrine Holde; John J McGrath; Veera Manikandan Rajagopal; Clara Albiñana; Bjarni Jóhann Vilhjálmsson; Jakob Grove; Esben Agerbo; Zeynep Yilmaz; Oleguer Plana-Ripoll; Trine Munk-Olsen; Ditte Demontis; Anders Børglum; Ole Mors; Cynthia M Bulik; Preben Bo Mortensen; Liselotte Vogdrup Petersen

doi:10.1016/j.biopsych.2023.11.020

Polygenic Risk of Mental Disorders and Subject-Specific School Grades

Biol Psychiatry. 2023 Dec 5:S0006-3223(23)01749-3. doi: 10.1016/j.biopsych.2023.11.020. Online ahead of print.

Authors

Oskar Hougaard Jefsen¹, Katrine Holde², John J McGrath³, Veera Manikandan Rajagopal⁴, Clara Albiñana⁵, Bjarni Jóhann Vilhjálmsson⁶, Jakob Grove⁷, Esben Agerbo⁸, Zeynep Yilmaz⁹, Oleguer Plana-Ripoll¹⁰, Trine Munk-Olsen¹¹, Ditte Demontis¹², Anders Børglum⁴, Ole Mors¹³, Cynthia M Bulik¹⁴, Preben Bo Mortensen⁵, Liselotte Vogdrup Petersen⁵

Affiliations

¹ Psychosis Research Unit, Aarhus University Hospital, Psychiatry, Aarhus, Denmark; Center of Functionally Integrative Neuroscience, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. Electronic address: oskar.jefsen@clin.au.dk.
² National Centre for Register-based Research, Aarhus University, Aarhus, Denmark.
³ National Centre for Register-based Research, Aarhus University, Aarhus, Denmark; Queensland Centre for Mental Health Research, Wacol, Queensland, Australia; Queensland Brain Institute, University of Queensland, St. Lucia, Brisbane, Queensland, Australia.
⁴ iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark; Department of Biomedicine, Aarhus University, Aarhus, Denmark; Center for Genomics and Personalized Medicine, Aarhus, Denmark; Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.
⁵ National Centre for Register-based Research, Aarhus University, Aarhus, Denmark; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.
⁶ National Centre for Register-based Research, Aarhus University, Aarhus, Denmark; Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark.
⁷ iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark; Department of Biomedicine, Aarhus University, Aarhus, Denmark; Center for Genomics and Personalized Medicine, Aarhus, Denmark; Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark; Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark.
⁸ National Centre for Register-based Research, Aarhus University, Aarhus, Denmark; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark; Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark; Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark.
⁹ National Centre for Register-based Research, Aarhus University, Aarhus, Denmark; Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
¹⁰ Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark.
¹¹ National Centre for Register-based Research, Aarhus University, Aarhus, Denmark; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark; Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark.
¹² iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark; Department of Biomedicine, Aarhus University, Aarhus, Denmark; Center for Genomics and Personalized Medicine, Aarhus, Denmark.
¹³ Psychosis Research Unit, Aarhus University Hospital, Psychiatry, Aarhus, Denmark.
¹⁴ Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

PMID: 38061465
DOI: 10.1016/j.biopsych.2023.11.020

Abstract

Background: Education is essential for socioeconomic security and long-term mental health; however, mental disorders are often detrimental to the educational trajectory. Genetic correlations between mental disorders and educational attainment do not always align with corresponding phenotypic associations, implying heterogeneity in the genetic overlap.

Methods: We unraveled this heterogeneity by investigating associations between polygenic risk scores for 6 mental disorders and fine-grained school outcomes: school grades in language and mathematics in ninth grade and high school, as well as educational attainment by age 25, using nationwide-representative data from established cohorts (N = 79,489).

Results: High polygenic liability of attention-deficit/hyperactivity disorder was associated with lower grades in language and mathematics, whereas high polygenic risk of anorexia nervosa or bipolar disorder was associated with higher grades in language and mathematics. Associations between polygenic risk and school grades were mixed for schizophrenia and major depressive disorder and neutral for autism spectrum disorder.

Conclusions: Polygenic risk scores for mental disorders are differentially associated with language and mathematics school grades.

Keywords: Educational attainment; Language; Mathematics; Mental disorders; Polygenic risk scores; School performance.