TY - JOUR

T1 - Identification of Gene Loci That Overlap Between Schizophrenia and Educational Attainment

AU - Le Hellard, Stéphanie

AU - Wang, Yunpeng

AU - Witoelar, Aree

AU - Zuber, Verena

AU - Bettella, Francesco

AU - Hugdahl, Kenneth

AU - Espeseth, Thomas

AU - Steen, Vidar M

AU - Melle, Ingrid

AU - Desikan, Rahul

AU - Schork, Andrew J

AU - Thompson, Wesley K

AU - Dale, Anders M

AU - Djurovic, Srdjan

AU - Andreassen, Ole A

AU - Knight, Jo

AU - Schizophrenia Working Group of the Psychiatric Genomics Consortium

N1 - This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Schizophrenia Bulletin following peer review. The definitive publisher-authenticated version Stéphanie Le Hellard, Yunpeng Wang, Aree Witoelar, Verena Zuber, Francesco Bettella, Kenneth Hugdahl, Thomas Espeseth, Vidar M. Steen, Ingrid Melle, Rahul Desikan, Andrew J. Schork, Wesley K. Thompson, Anders M. Dale, Srdjan Djurovic, Ole A. Andreassen, ; Identification of Gene Loci That Overlap Between Schizophrenia and Educational Attainment, Schizophrenia Bulletin, Volume 43, Issue 3, 1 May 2017, Pages 654–664, https://doi.org/10.1093/schbul/sbw085 is available online at: https://academic.oup.com/schizophreniabulletin/article/43/3/654/2511172

PY - 2016/6/26

Y1 - 2016/6/26

N2 - 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.

AB - 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.

KW - Adult

KW - Aptitude

KW - Educational Status

KW - Female

KW - Genetic Loci

KW - Genome-Wide Association Study

KW - Humans

KW - Male

KW - Multifactorial Inheritance

KW - Polymorphism, Single Nucleotide

KW - Schizophrenia

KW - Journal Article

U2 - 10.1093/schbul/sbw085

DO - 10.1093/schbul/sbw085

M3 - Journal article

C2 - 27338279

VL - 43

SP - 654

EP - 664

JO - Schizophrenia Bulletin

JF - Schizophrenia Bulletin

SN - 0586-7614

IS - 3

ER -