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Two non-synonymous markers in PTPN21, identified by genome-wide association study data-mining and replication, are associated with schizophrenia.
Chen, Jingchun Lee, Grace Fanous, Ayman H Zhao, Zhongming Jia, Peilin O'Neill, Anthony Walsh, Dermot Kendler, Kenneth S Chen, Xiangning
Chen, Jingchun
Lee, Grace
Fanous, Ayman H
Zhao, Zhongming
Jia, Peilin
O'Neill, Anthony
Walsh, Dermot
Kendler, Kenneth S
Chen, Xiangning
Advisors
Editors
Other Contributors
Date
2011-09
Date Submitted
Keywords
Other Subjects
Subject 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
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
Planned Date
Start Date
Collaborators
Principal Investigators
Alternative Titles
Publisher
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.
Language
en
ISSN
1573-2509
eISSN
ISBN
DOI
10.1016/j.schres.2011.06.023
PMID
21752600