Replication of previous genome-wide association studies of psychiatric diseases in a large schizophrenia case-control sample from Spain

José Luis Ivorra; Olga Rivero; Javier Costas; Raquel Iniesta; Manuel Arrojo; Ramón Ramos-Ríos; Ángel Carracedo; Tomas Palomo; Roberto Rodriguez-Jimenez; Jorge Cervilla; Blanca Gutiérrez; Esther Molina; Celso Arango; Mar Álvarez; Juan C. Pascual; Víctor Pérez; Pilar Alejandra Saiz; María Paz García-Portilla; Julio Bobes; Ana González-Pinto; Iñaki Zorrilla; Josep María Haro; Miguel Bernardo; Enrique Baca-García; José Carlos González; Janet Hoenicka; María Dolores Moltó; Julio Sanjuán

doi:10.1016/j.schres.2014.07.004

Replication of previous genome-wide association studies of psychiatric diseases in a large schizophrenia case-control sample from Spain

José Luis Ivorra, Olga Rivero, Javier Costas, Raquel Iniesta, Manuel Arrojo, Ramón Ramos-Ríos, Ángel Carracedo, Tomas Palomo, Roberto Rodriguez-Jimenez, Jorge Cervilla, Blanca Gutiérrez, Esther Molina, Celso Arango, Mar Álvarez, Juan C. Pascual, Víctor Pérez, Pilar Alejandra Saiz, María Paz García-Portilla, Julio Bobes, Ana González-PintoIñaki Zorrilla, Josep María Haro, Miguel Bernardo, Enrique Baca-García, José Carlos González, Janet Hoenicka, María Dolores Moltó, Julio Sanjuán

Social Genetic & Developmental Psychiatry

Research output: Contribution to journal › Article › peer-review

29 Citations (Scopus)

Abstract

Genome wide association studies (GWAS) has allowed the discovery of some interesting risk variants for schizophrenia (SCZ). However, this high-throughput approach presents some limitations, being the most important the necessity of highly restrictive statistical corrections as well as the loss of statistical power inherent to the use of a Single Nucleotide Polymorphism (SNP) analysis approach. These problems can be partially solved through the use of a polygenic approach. We performed a genotyping study in SCZ using 86 previously associated SNPs identified by GWAS of SCZ, bipolar disorder (BPD) and autistic spectrum disorder (ASD) patients. The sample consisted of 3063 independent cases with DSM-IV-TR diagnosis of SCZ and 2847 independent controls of European origin from Spain. A polygenic score analysis was also used to test the overall effect on the SCZ status. One SNP, rs12290811, located in the ODZ4 gene reached statistical significance (p=1.7×10(-4), Allelic odds ratio=1.21), a value very near to those reported in previous GWAS of BPD patients. In addition, 4 SNPs were close to the significant threshold: rs3850333, in the NRXN1 gene; rs6932590, at MHC; rs2314398, located in an intergenic region on chromosome 2; and rs1006737, in the CACNA1C gene. We also found that 74% of the studied SNPs showed the same tendency (risk or protection alleles) previously reported in the original GWAS (p<0.001). Our data strengthen the polygenic component of susceptibility to SCZ. Our findings show ODZ4 as a risk gene for SCZ, emphasizing the existence of common vulnerability in psychosis.

Original language	English
Pages (from-to)	107-113
Journal	Schizophrenia Research
Volume	159
Issue number	1
Early online date	12 Aug 2014
DOIs	https://doi.org/10.1016/j.schres.2014.07.004
Publication status	Published - Oct 2014

Keywords

Adolescent
Adult
Aged
Aged, 80 and over
Area Under Curve
Case-Control Studies
European Continental Ancestry Group
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Male
Membrane Glycoproteins
Middle Aged
Models, Genetic
Multifactorial Inheritance
Polymorphism, Single Nucleotide
ROC Curve
Schizophrenia
Spain
Young Adult

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10.1016/j.schres.2014.07.004

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Ivorra, J. L., Rivero, O., Costas, J., Iniesta, R., Arrojo, M., Ramos-Ríos, R., Carracedo, Á., Palomo, T., Rodriguez-Jimenez, R., Cervilla, J., Gutiérrez, B., Molina, E., Arango, C., Álvarez, M., Pascual, J. C., Pérez, V., Saiz, P. A., García-Portilla, M. P., Bobes, J., ... Sanjuán, J. (2014). Replication of previous genome-wide association studies of psychiatric diseases in a large schizophrenia case-control sample from Spain. Schizophrenia Research, 159(1), 107-113. https://doi.org/10.1016/j.schres.2014.07.004

@article{31afe479a2344d4c961239c2b3ad1e1d,

title = "Replication of previous genome-wide association studies of psychiatric diseases in a large schizophrenia case-control sample from Spain",

abstract = "Genome wide association studies (GWAS) has allowed the discovery of some interesting risk variants for schizophrenia (SCZ). However, this high-throughput approach presents some limitations, being the most important the necessity of highly restrictive statistical corrections as well as the loss of statistical power inherent to the use of a Single Nucleotide Polymorphism (SNP) analysis approach. These problems can be partially solved through the use of a polygenic approach. We performed a genotyping study in SCZ using 86 previously associated SNPs identified by GWAS of SCZ, bipolar disorder (BPD) and autistic spectrum disorder (ASD) patients. The sample consisted of 3063 independent cases with DSM-IV-TR diagnosis of SCZ and 2847 independent controls of European origin from Spain. A polygenic score analysis was also used to test the overall effect on the SCZ status. One SNP, rs12290811, located in the ODZ4 gene reached statistical significance (p=1.7×10(-4), Allelic odds ratio=1.21), a value very near to those reported in previous GWAS of BPD patients. In addition, 4 SNPs were close to the significant threshold: rs3850333, in the NRXN1 gene; rs6932590, at MHC; rs2314398, located in an intergenic region on chromosome 2; and rs1006737, in the CACNA1C gene. We also found that 74% of the studied SNPs showed the same tendency (risk or protection alleles) previously reported in the original GWAS (p<0.001). Our data strengthen the polygenic component of susceptibility to SCZ. Our findings show ODZ4 as a risk gene for SCZ, emphasizing the existence of common vulnerability in psychosis.",

keywords = "Adolescent, Adult, Aged, Aged, 80 and over, Area Under Curve, Case-Control Studies, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Membrane Glycoproteins, Middle Aged, Models, Genetic, Multifactorial Inheritance, Polymorphism, Single Nucleotide, ROC Curve, Schizophrenia, Spain, Young Adult",

author = "Ivorra, {Jos{\'e} Luis} and Olga Rivero and Javier Costas and Raquel Iniesta and Manuel Arrojo and Ram{\'o}n Ramos-R{\'i}os and {\'A}ngel Carracedo and Tomas Palomo and Roberto Rodriguez-Jimenez and Jorge Cervilla and Blanca Guti{\'e}rrez and Esther Molina and Celso Arango and Mar {\'A}lvarez and Pascual, {Juan C.} and V{\'i}ctor P{\'e}rez and Saiz, {Pilar Alejandra} and Garc{\'i}a-Portilla, {Mar{\'i}a Paz} and Julio Bobes and Ana Gonz{\'a}lez-Pinto and I{\~n}aki Zorrilla and Haro, {Josep Mar{\'i}a} and Miguel Bernardo and Enrique Baca-Garc{\'i}a and Gonz{\'a}lez, {Jos{\'e} Carlos} and Janet Hoenicka and Molt{\'o}, {Mar{\'i}a Dolores} and Julio Sanju{\'a}n",

note = "Copyright {\textcopyright} 2014. Published by Elsevier B.V.",

year = "2014",

month = oct,

doi = "10.1016/j.schres.2014.07.004",

language = "English",

volume = "159",

pages = "107--113",

journal = "Schizophrenia Research",

issn = "0920-9964",

publisher = "Elsevier",

number = "1",

}

Ivorra, JL, Rivero, O, Costas, J, Iniesta, R, Arrojo, M, Ramos-Ríos, R, Carracedo, Á, Palomo, T, Rodriguez-Jimenez, R, Cervilla, J, Gutiérrez, B, Molina, E, Arango, C, Álvarez, M, Pascual, JC, Pérez, V, Saiz, PA, García-Portilla, MP, Bobes, J, González-Pinto, A, Zorrilla, I, Haro, JM, Bernardo, M, Baca-García, E, González, JC, Hoenicka, J, Moltó, MD & Sanjuán, J 2014, 'Replication of previous genome-wide association studies of psychiatric diseases in a large schizophrenia case-control sample from Spain', Schizophrenia Research, vol. 159, no. 1, pp. 107-113. https://doi.org/10.1016/j.schres.2014.07.004

TY - JOUR

T1 - Replication of previous genome-wide association studies of psychiatric diseases in a large schizophrenia case-control sample from Spain

AU - Ivorra, José Luis

AU - Rivero, Olga

AU - Costas, Javier

AU - Iniesta, Raquel

AU - Arrojo, Manuel

AU - Ramos-Ríos, Ramón

AU - Carracedo, Ángel

AU - Palomo, Tomas

AU - Rodriguez-Jimenez, Roberto

AU - Cervilla, Jorge

AU - Gutiérrez, Blanca

AU - Molina, Esther

AU - Arango, Celso

AU - Álvarez, Mar

AU - Pascual, Juan C.

AU - Pérez, Víctor

AU - Saiz, Pilar Alejandra

AU - García-Portilla, María Paz

AU - Bobes, Julio

AU - González-Pinto, Ana

AU - Zorrilla, Iñaki

AU - Haro, Josep María

AU - Bernardo, Miguel

AU - Baca-García, Enrique

AU - González, José Carlos

AU - Hoenicka, Janet

AU - Moltó, María Dolores

AU - Sanjuán, Julio

PY - 2014/10

Y1 - 2014/10

N2 - Genome wide association studies (GWAS) has allowed the discovery of some interesting risk variants for schizophrenia (SCZ). However, this high-throughput approach presents some limitations, being the most important the necessity of highly restrictive statistical corrections as well as the loss of statistical power inherent to the use of a Single Nucleotide Polymorphism (SNP) analysis approach. These problems can be partially solved through the use of a polygenic approach. We performed a genotyping study in SCZ using 86 previously associated SNPs identified by GWAS of SCZ, bipolar disorder (BPD) and autistic spectrum disorder (ASD) patients. The sample consisted of 3063 independent cases with DSM-IV-TR diagnosis of SCZ and 2847 independent controls of European origin from Spain. A polygenic score analysis was also used to test the overall effect on the SCZ status. One SNP, rs12290811, located in the ODZ4 gene reached statistical significance (p=1.7×10(-4), Allelic odds ratio=1.21), a value very near to those reported in previous GWAS of BPD patients. In addition, 4 SNPs were close to the significant threshold: rs3850333, in the NRXN1 gene; rs6932590, at MHC; rs2314398, located in an intergenic region on chromosome 2; and rs1006737, in the CACNA1C gene. We also found that 74% of the studied SNPs showed the same tendency (risk or protection alleles) previously reported in the original GWAS (p<0.001). Our data strengthen the polygenic component of susceptibility to SCZ. Our findings show ODZ4 as a risk gene for SCZ, emphasizing the existence of common vulnerability in psychosis.

AB - Genome wide association studies (GWAS) has allowed the discovery of some interesting risk variants for schizophrenia (SCZ). However, this high-throughput approach presents some limitations, being the most important the necessity of highly restrictive statistical corrections as well as the loss of statistical power inherent to the use of a Single Nucleotide Polymorphism (SNP) analysis approach. These problems can be partially solved through the use of a polygenic approach. We performed a genotyping study in SCZ using 86 previously associated SNPs identified by GWAS of SCZ, bipolar disorder (BPD) and autistic spectrum disorder (ASD) patients. The sample consisted of 3063 independent cases with DSM-IV-TR diagnosis of SCZ and 2847 independent controls of European origin from Spain. A polygenic score analysis was also used to test the overall effect on the SCZ status. One SNP, rs12290811, located in the ODZ4 gene reached statistical significance (p=1.7×10(-4), Allelic odds ratio=1.21), a value very near to those reported in previous GWAS of BPD patients. In addition, 4 SNPs were close to the significant threshold: rs3850333, in the NRXN1 gene; rs6932590, at MHC; rs2314398, located in an intergenic region on chromosome 2; and rs1006737, in the CACNA1C gene. We also found that 74% of the studied SNPs showed the same tendency (risk or protection alleles) previously reported in the original GWAS (p<0.001). Our data strengthen the polygenic component of susceptibility to SCZ. Our findings show ODZ4 as a risk gene for SCZ, emphasizing the existence of common vulnerability in psychosis.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Area Under Curve

KW - Case-Control Studies

KW - European Continental Ancestry Group

KW - Female

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Male

KW - Membrane Glycoproteins

KW - Middle Aged

KW - Models, Genetic

KW - Multifactorial Inheritance

KW - Polymorphism, Single Nucleotide

KW - ROC Curve

KW - Schizophrenia

KW - Spain

KW - Young Adult

U2 - 10.1016/j.schres.2014.07.004

DO - 10.1016/j.schres.2014.07.004

M3 - Article

C2 - 25124521

SN - 0920-9964

VL - 159

SP - 107

EP - 113

JO - Schizophrenia Research

JF - Schizophrenia Research

IS - 1

ER -

Replication of previous genome-wide association studies of psychiatric diseases in a large schizophrenia case-control sample from Spain

Abstract

Keywords

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