Association Study of Nonsynonymous Single Nucleotide Polymorphisms in Schizophrenia

Noa Carrera; Manuel Arrojo; Julio Sanjuan; Ramon Ramos-Rios; Eduardo Paz; Jose J. Suarez-Rama; Mario Paramo; Santiago Agra; Julio Brenlla; Silvia Martinez; Olga Rivero; David A. Collier; Aarno Palotie; Sven Cichon; Markus M. Noethen; Marcella Rietschel; Dan Rujescu; Hreinn Stefansson; Stacy Steinberg; Engilbert Sigurdsson; David St Clair; Sarah Tosato; Thomas Werge; Kari Stefansson; Jose Carlos Gonzalez; Joaquin Valero; Alfonso Gutierez-Zotes; Antonio Labad; Lourdes Martorell; Elisabet Vilella; Angel Carracedo; Javier Costas

doi:10.1016/j.biopsych.2011.09.032

Association Study of Nonsynonymous Single Nucleotide Polymorphisms in Schizophrenia

Noa Carrera, Manuel Arrojo, Julio Sanjuan, Ramon Ramos-Rios, Eduardo Paz, Jose J. Suarez-Rama, Mario Paramo, Santiago Agra, Julio Brenlla, Silvia Martinez, Olga Rivero, David A. Collier, Aarno Palotie, Sven Cichon, Markus M. Noethen, Marcella Rietschel, Dan Rujescu, Hreinn Stefansson, Stacy Steinberg, Engilbert SigurdssonDavid St Clair, Sarah Tosato, Thomas Werge, Kari Stefansson, Jose Carlos Gonzalez, Joaquin Valero, Alfonso Gutierez-Zotes, Antonio Labad, Lourdes Martorell, Elisabet Vilella, Angel Carracedo, Javier Costas

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Abstract

Background: Genome-wide association studies using several hundred thousand anonymous markers present limited statistical power. Alternatively, association studies restricted to common nonsynonymous single nucleotide polymorphisms (nsSNPs) have the advantage of strongly reducing the multiple testing problem, while increasing the probability of testing functional single nucleotide polymorphisms (SNPs). Methods: We performed a case-control association study of common nsSNPs in Galician (northwest Spain) samples using the Affymetrix GeneChip Human 20k cSNP Kit, followed by a replication study of the more promising results. After quality control procedures, the discovery sample consisted of 5100 nsSNPs at minor allele frequency >5% analyzed in 476 schizophrenia patients and 447 control subjects. The replication sample consisted of 4069 cases and 15,128 control subjects of European origin. We also performed multilocus analysis, using aggregated scores of nsSNPs at liberal significance thresholds and cross-validation procedures. Results: The 5 independent nsSNPs with false discovery rate q

Original language	English
Pages (from-to)	169 - 177
Number of pages	9
Journal	Biological psychiatry
Volume	71
Issue number	2
DOIs	https://doi.org/10.1016/j.biopsych.2011.09.032
Publication status	Published - 15 Jan 2012

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Carrera, N., Arrojo, M., Sanjuan, J., Ramos-Rios, R., Paz, E., Suarez-Rama, J. J., Paramo, M., Agra, S., Brenlla, J., Martinez, S., Rivero, O., Collier, D. A., Palotie, A., Cichon, S., Noethen, M. M., Rietschel, M., Rujescu, D., Stefansson, H., Steinberg, S., ... Costas, J. (2012). Association Study of Nonsynonymous Single Nucleotide Polymorphisms in Schizophrenia. Biological psychiatry, 71(2), 169 - 177. https://doi.org/10.1016/j.biopsych.2011.09.032

@article{ae04e3f1db49429fa4d85fcc7ecc6ebb,

title = "Association Study of Nonsynonymous Single Nucleotide Polymorphisms in Schizophrenia",

abstract = "Background: Genome-wide association studies using several hundred thousand anonymous markers present limited statistical power. Alternatively, association studies restricted to common nonsynonymous single nucleotide polymorphisms (nsSNPs) have the advantage of strongly reducing the multiple testing problem, while increasing the probability of testing functional single nucleotide polymorphisms (SNPs). Methods: We performed a case-control association study of common nsSNPs in Galician (northwest Spain) samples using the Affymetrix GeneChip Human 20k cSNP Kit, followed by a replication study of the more promising results. After quality control procedures, the discovery sample consisted of 5100 nsSNPs at minor allele frequency >5% analyzed in 476 schizophrenia patients and 447 control subjects. The replication sample consisted of 4069 cases and 15,128 control subjects of European origin. We also performed multilocus analysis, using aggregated scores of nsSNPs at liberal significance thresholds and cross-validation procedures. Results: The 5 independent nsSNPs with false discovery rate q ",

author = "Noa Carrera and Manuel Arrojo and Julio Sanjuan and Ramon Ramos-Rios and Eduardo Paz and Suarez-Rama, {Jose J.} and Mario Paramo and Santiago Agra and Julio Brenlla and Silvia Martinez and Olga Rivero and Collier, {David A.} and Aarno Palotie and Sven Cichon and Noethen, {Markus M.} and Marcella Rietschel and Dan Rujescu and Hreinn Stefansson and Stacy Steinberg and Engilbert Sigurdsson and {St Clair}, David and Sarah Tosato and Thomas Werge and Kari Stefansson and {Carlos Gonzalez}, Jose and Joaquin Valero and Alfonso Gutierez-Zotes and Antonio Labad and Lourdes Martorell and Elisabet Vilella and Angel Carracedo and Javier Costas",

year = "2012",

month = jan,

day = "15",

doi = "10.1016/j.biopsych.2011.09.032",

language = "English",

volume = "71",

pages = "169 -- 177",

journal = "Biological psychiatry",

issn = "1873-2402",

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Carrera, N, Arrojo, M, Sanjuan, J, Ramos-Rios, R, Paz, E, Suarez-Rama, JJ, Paramo, M, Agra, S, Brenlla, J, Martinez, S, Rivero, O, Collier, DA, Palotie, A, Cichon, S, Noethen, MM, Rietschel, M, Rujescu, D, Stefansson, H, Steinberg, S, Sigurdsson, E, St Clair, D, Tosato, S, Werge, T, Stefansson, K, Carlos Gonzalez, J, Valero, J, Gutierez-Zotes, A, Labad, A, Martorell, L, Vilella, E, Carracedo, A & Costas, J 2012, 'Association Study of Nonsynonymous Single Nucleotide Polymorphisms in Schizophrenia', Biological psychiatry, vol. 71, no. 2, pp. 169 - 177. https://doi.org/10.1016/j.biopsych.2011.09.032

TY - JOUR

T1 - Association Study of Nonsynonymous Single Nucleotide Polymorphisms in Schizophrenia

AU - Carrera, Noa

AU - Arrojo, Manuel

AU - Sanjuan, Julio

AU - Ramos-Rios, Ramon

AU - Paz, Eduardo

AU - Suarez-Rama, Jose J.

AU - Paramo, Mario

AU - Agra, Santiago

AU - Brenlla, Julio

AU - Martinez, Silvia

AU - Rivero, Olga

AU - Collier, David A.

AU - Palotie, Aarno

AU - Cichon, Sven

AU - Noethen, Markus M.

AU - Rietschel, Marcella

AU - Rujescu, Dan

AU - Stefansson, Hreinn

AU - Steinberg, Stacy

AU - Sigurdsson, Engilbert

AU - St Clair, David

AU - Tosato, Sarah

AU - Werge, Thomas

AU - Stefansson, Kari

AU - Carlos Gonzalez, Jose

AU - Valero, Joaquin

AU - Gutierez-Zotes, Alfonso

AU - Labad, Antonio

AU - Martorell, Lourdes

AU - Vilella, Elisabet

AU - Carracedo, Angel

AU - Costas, Javier

PY - 2012/1/15

Y1 - 2012/1/15

N2 - Background: Genome-wide association studies using several hundred thousand anonymous markers present limited statistical power. Alternatively, association studies restricted to common nonsynonymous single nucleotide polymorphisms (nsSNPs) have the advantage of strongly reducing the multiple testing problem, while increasing the probability of testing functional single nucleotide polymorphisms (SNPs). Methods: We performed a case-control association study of common nsSNPs in Galician (northwest Spain) samples using the Affymetrix GeneChip Human 20k cSNP Kit, followed by a replication study of the more promising results. After quality control procedures, the discovery sample consisted of 5100 nsSNPs at minor allele frequency >5% analyzed in 476 schizophrenia patients and 447 control subjects. The replication sample consisted of 4069 cases and 15,128 control subjects of European origin. We also performed multilocus analysis, using aggregated scores of nsSNPs at liberal significance thresholds and cross-validation procedures. Results: The 5 independent nsSNPs with false discovery rate q

AB - Background: Genome-wide association studies using several hundred thousand anonymous markers present limited statistical power. Alternatively, association studies restricted to common nonsynonymous single nucleotide polymorphisms (nsSNPs) have the advantage of strongly reducing the multiple testing problem, while increasing the probability of testing functional single nucleotide polymorphisms (SNPs). Methods: We performed a case-control association study of common nsSNPs in Galician (northwest Spain) samples using the Affymetrix GeneChip Human 20k cSNP Kit, followed by a replication study of the more promising results. After quality control procedures, the discovery sample consisted of 5100 nsSNPs at minor allele frequency >5% analyzed in 476 schizophrenia patients and 447 control subjects. The replication sample consisted of 4069 cases and 15,128 control subjects of European origin. We also performed multilocus analysis, using aggregated scores of nsSNPs at liberal significance thresholds and cross-validation procedures. Results: The 5 independent nsSNPs with false discovery rate q

U2 - 10.1016/j.biopsych.2011.09.032

DO - 10.1016/j.biopsych.2011.09.032

M3 - Article

SN - 1873-2402

VL - 71

SP - 169

EP - 177

JO - Biological psychiatry

JF - Biological psychiatry

IS - 2

ER -

Association Study of Nonsynonymous Single Nucleotide Polymorphisms in Schizophrenia

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