Two non-synonymous markers in PTPN21, identified by genome-wide association study data-mining and replication, are associated with schizophrenia.

Hdl Handle:
http://hdl.handle.net/10147/238797
Title:
Two non-synonymous markers in PTPN21, identified by genome-wide association study data-mining and replication, are associated with schizophrenia.
Authors:
Chen, Jingchun; Lee, Grace; Fanous, Ayman H; Zhao, Zhongming; Jia, Peilin; O'Neill, Anthony; Walsh, Dermot; Kendler, Kenneth S; Chen, Xiangning
Affiliation:
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Suite 390, 800 E. Leigh Street, Richmond, VA 23298, USA.
Citation:
Two non-synonymous markers in PTPN21, identified by genome-wide association study data-mining and replication, are associated with schizophrenia. 2011, 131 (1-3):43-51 Schizophr. Res.
Journal:
Schizophrenia research
Issue Date:
Sep-2011
URI:
http://hdl.handle.net/10147/238797
DOI:
10.1016/j.schres.2011.06.023
PubMed ID:
21752600
Abstract:
We conducted data-mining analyses of genome wide association (GWA) studies of the CATIE and MGS-GAIN datasets, and found 13 markers in the two physically linked genes, PTPN21 and EML5, showing nominally significant association with schizophrenia. Linkage disequilibrium (LD) analysis indicated that all 7 markers from PTPN21 shared high LD (r(2)>0.8), including rs2274736 and rs2401751, the two non-synonymous markers with the most significant association signals (rs2401751, P=1.10 × 10(-3) and rs2274736, P=1.21 × 10(-3)). In a meta-analysis of all 13 replication datasets with a total of 13,940 subjects, we found that the two non-synonymous markers are significantly associated with schizophrenia (rs2274736, OR=0.92, 95% CI: 0.86-0.97, P=5.45 × 10(-3) and rs2401751, OR=0.92, 95% CI: 0.86-0.97, P=5.29 × 10(-3)). One SNP (rs7147796) in EML5 is also significantly associated with the disease (OR=1.08, 95% CI: 1.02-1.14, P=6.43 × 10(-3)). These 3 markers remain significant after Bonferroni correction. Furthermore, haplotype conditioned analyses indicated that the association signals observed between rs2274736/rs2401751 and rs7147796 are statistically independent. Given the results that 2 non-synonymous markers in PTPN21 are associated with schizophrenia, further investigation of this locus is warranted.
Item Type:
Article
Language:
en
MeSH:
Computational Biology; Databases, Genetic; Gene Frequency; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Linkage Disequilibrium; Meta-Analysis as Topic; Microtubule-Associated Proteins; Polymorphism, Single Nucleotide; Protein Tyrosine Phosphatases, Non-Receptor; Schizophrenia
ISSN:
1573-2509

Full metadata record

DC FieldValue Language
dc.contributor.authorChen, Jingchunen_GB
dc.contributor.authorLee, Graceen_GB
dc.contributor.authorFanous, Ayman Hen_GB
dc.contributor.authorZhao, Zhongmingen_GB
dc.contributor.authorJia, Peilinen_GB
dc.contributor.authorO'Neill, Anthonyen_GB
dc.contributor.authorWalsh, Dermoten_GB
dc.contributor.authorKendler, Kenneth Sen_GB
dc.contributor.authorChen, Xiangningen_GB
dc.date.accessioned2012-08-15T14:13:07Z-
dc.date.available2012-08-15T14:13:07Z-
dc.date.issued2011-09-
dc.identifier.citationTwo non-synonymous markers in PTPN21, identified by genome-wide association study data-mining and replication, are associated with schizophrenia. 2011, 131 (1-3):43-51 Schizophr. Res.en_GB
dc.identifier.issn1573-2509-
dc.identifier.pmid21752600-
dc.identifier.doi10.1016/j.schres.2011.06.023-
dc.identifier.urihttp://hdl.handle.net/10147/238797-
dc.description.abstractWe conducted data-mining analyses of genome wide association (GWA) studies of the CATIE and MGS-GAIN datasets, and found 13 markers in the two physically linked genes, PTPN21 and EML5, showing nominally significant association with schizophrenia. Linkage disequilibrium (LD) analysis indicated that all 7 markers from PTPN21 shared high LD (r(2)>0.8), including rs2274736 and rs2401751, the two non-synonymous markers with the most significant association signals (rs2401751, P=1.10 × 10(-3) and rs2274736, P=1.21 × 10(-3)). In a meta-analysis of all 13 replication datasets with a total of 13,940 subjects, we found that the two non-synonymous markers are significantly associated with schizophrenia (rs2274736, OR=0.92, 95% CI: 0.86-0.97, P=5.45 × 10(-3) and rs2401751, OR=0.92, 95% CI: 0.86-0.97, P=5.29 × 10(-3)). One SNP (rs7147796) in EML5 is also significantly associated with the disease (OR=1.08, 95% CI: 1.02-1.14, P=6.43 × 10(-3)). These 3 markers remain significant after Bonferroni correction. Furthermore, haplotype conditioned analyses indicated that the association signals observed between rs2274736/rs2401751 and rs7147796 are statistically independent. Given the results that 2 non-synonymous markers in PTPN21 are associated with schizophrenia, further investigation of this locus is warranted.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Schizophrenia researchen_GB
dc.subject.meshComputational Biology-
dc.subject.meshDatabases, Genetic-
dc.subject.meshGene Frequency-
dc.subject.meshGenetic Predisposition to Disease-
dc.subject.meshGenome-Wide Association Study-
dc.subject.meshHumans-
dc.subject.meshLinkage Disequilibrium-
dc.subject.meshMeta-Analysis as Topic-
dc.subject.meshMicrotubule-Associated Proteins-
dc.subject.meshPolymorphism, Single Nucleotide-
dc.subject.meshProtein Tyrosine Phosphatases, Non-Receptor-
dc.subject.meshSchizophrenia-
dc.titleTwo non-synonymous markers in PTPN21, identified by genome-wide association study data-mining and replication, are associated with schizophrenia.en_GB
dc.typeArticleen
dc.contributor.departmentVirginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Suite 390, 800 E. Leigh Street, Richmond, VA 23298, USA.en_GB
dc.identifier.journalSchizophrenia researchen_GB
dc.description.provinceLeinsteren

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