Two non-synonymous markers in PTPN21, identified by genome-wide association study data-mining and replication, are associated with schizophrenia.
Fanous, Ayman H
Kendler, Kenneth S
AffiliationVirginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Suite 390, 800 E. Leigh Street, Richmond, VA 23298, USA.
Genetic Predisposition to Disease
Genome-Wide Association Study
Meta-Analysis as Topic
Polymorphism, Single Nucleotide
Protein Tyrosine Phosphatases, Non-Receptor
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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.
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.
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