title: Identification of Gene Loci That Overlap Between Schizophrenia and Educational Attainment.
abstract: There is evidence for genetic overlap between cognitive abilities and schizophrenia (SCZ), and genome-wide association studies (GWAS) demonstrate that both SCZ and general cognitive abilities have a strong polygenic component with many single-nucleotide polymorphisms (SNPs) each with a small effect. Here we investigated the shared genetic architecture between SCZ and educational attainment, which is regarded as a "proxy phenotype" for cognitive abilities, but may also reflect other traits. We applied a conditional false discovery rate (condFDR) method to GWAS of SCZ (n = 82 315), college completion ("College," n = 95 427), and years of education ("EduYears," n = 101 069). Variants associated with College or EduYears showed enrichment of association with SCZ, demonstrating polygenic overlap. This was confirmed by an increased replication rate in SCZ. By applying a condFDR threshold <0.01, we identified 18 genomic loci associated with SCZ after conditioning on College and 15 loci associated with SCZ after conditioning on EduYears. Ten of these loci overlapped. Using conjunctional FDR, we identified 10 loci shared between SCZ and College, and 29 loci shared between SCZ and EduYears. The majority of these loci had effects in opposite directions. Our results provide evidence for polygenic overlap between SCZ and educational attainment, and identify novel pleiotropic loci. Other studies have reported genetic overlap between SCZ and cognition, or SCZ and educational attainment, with negative correlation. Importantly, our methods enable identification of bi-directional effects, which highlight the complex relationship between SCZ and educational attainment, and support polygenic mechanisms underlying both cognitive dysfunction and creativity in SCZ.
authors.affiliation: NORMENT-KG Jebsen Centre, Department of Clinical Science, University of Bergen, Bergen, Norway.|Dr Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Le Hellard
authors.affiliation: NORMENT-KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|NORMENT-KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.|Multimodal Imaging Lab, University of California at San Diego, La Jolla, CA, USA.|Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: NORMENT-KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|NORMENT-KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors.forename: Aree
authors.initials: A
authors.lastname: Witoelar
authors.affiliation: NORMENT-KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|NORMENT-KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.|NCMM, University of Oslo, Oslo, Norway.
authors.forename: Verena
authors.initials: V
authors.lastname: Zuber
authors.affiliation: NORMENT-KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|NORMENT-KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bettella
authors.affiliation: NORMENT, Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.|Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hugdahl
authors.affiliation: NORMENT-KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.|Department of Psychology, University of Oslo, Oslo, Norway.
authors.forename: Thomas
authors.initials: T
authors.lastname: Espeseth
authors.affiliation: NORMENT-KG Jebsen Centre, Department of Clinical Science, University of Bergen, Bergen, Norway.|Dr Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Vidar M
authors.initials: VM
authors.lastname: Steen
authors.affiliation: NORMENT-KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|NORMENT-KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Melle
authors.affiliation: Multimodal Imaging Lab, University of California at San Diego, La Jolla, CA, USA.|Department of Radiology, University of California at San Diego, La Jolla, CA, USA.
authors.forename: Rahul
authors.initials: R
authors.lastname: Desikan
authors.affiliation: Multimodal Imaging Lab, University of California at San Diego, La Jolla, CA, USA.|Department of Cognitive Science, University of California San Diego, La Jolla, CA, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Schork
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Wesley K
authors.initials: WK
authors.lastname: Thompson
authors.affiliation: Multimodal Imaging Lab, University of California at San Diego, La Jolla, CA, USA.|Department of Cognitive Science, University of California San Diego, La Jolla, CA, USA.|Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
authors.forename: Anders M
authors.initials: AM
authors.lastname: Dale
authors.affiliation: NORMENT-KG Jebsen Centre, Department of Clinical Science, University of Bergen, Bergen, Norway.|NORMENT-KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.|Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Srdjan
authors.initials: S
authors.lastname: Djurovic
authors.affiliation: NORMENT-KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|NORMENT-KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.|Multimodal Imaging Lab, University of California at San Diego, La Jolla, CA, USA.
authors.forename: Ole A
authors.initials: OA
authors.lastname: Andreassen
mesh_terms: D000328:Adult; D001076:Aptitude; D004522:Educational Status; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D020412:Multifactorial Inheritance; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*
keywords: GWAS; conditional FDR; pleiotropy