Identification of Gene Loci That Overlap Between Schizophrenia and Educational Attainment
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Identification of Gene Loci That Overlap Between Schizophrenia and Educational Attainment. / Le Hellard, Stéphanie; Wang, Yunpeng; Witoelar, Aree; Zuber, Verena; Bettella, Francesco; Hugdahl, Kenneth; Espeseth, Thomas; Steen, Vidar M; Melle, Ingrid; Desikan, Rahul; Schork, Andrew J; Thompson, Wesley K; Dale, Anders M; Djurovic, Srdjan; Andreassen, Ole A; Schizophrenia Working Group of the Psychiatric Genomics Consortium; Ripke, Stephan; Neale, Benjamin M; Corvin, Aiden; Pers, Tune H; Agerbo, Esben; Demontis, Ditte; Hansen, Thomas; Hollegaard, Mads V; Hougaard, David M.; Mors, Ole; Børglum, Anders D; Werge, Thomas; Daly, Mark J; Sullivan, Patrick F; O'Donovan, Michael C.
I: Schizophrenia Bulletin, Bind 43, Nr. 3, 2017, s. 654-664.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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 - Schizophrenia Working Group of the Psychiatric Genomics Consortium
AU - Ripke, Stephan
AU - Neale, Benjamin M
AU - Corvin, Aiden
AU - Pers, Tune H
AU - Agerbo, Esben
AU - Demontis, Ditte
AU - Hansen, Thomas
AU - Hollegaard, Mads V
AU - Hougaard, David M.
AU - Mors, Ole
AU - Børglum, Anders D
AU - Werge, Thomas
AU - Daly, Mark J
AU - Sullivan, Patrick F
AU - O'Donovan, Michael C
N1 - © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.
PY - 2017
Y1 - 2017
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/genetics
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 -
ID: 195190365