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

• Published in: Schizophrenia research Vol. 131; no. 1; pp. 43 - 51
• Main Authors: Chen, Jingchun, Lee, Grace, Fanous, Ayman H, Zhao, Zhongming, Jia, Peilin, O'Neill, Anthony, Walsh, Dermot, Kendler, Kenneth S, Chen, Xiangning, The International Schizophrenia Consortium
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.09.2011; Elsevier
• Subjects: Adult and adolescent clinical studies; Biological and medical sciences; Computational Biology - methods; Computational Biology - statistics & numerical data; Data-mining; Databases, Genetic - statistics & numerical data; Gene Frequency; Genetic association study; Genetic Predisposition to Disease - genetics; Genome-Wide Association Study; Humans; Informatic prioritization; Linkage Disequilibrium; Medical sciences; Meta-Analysis as Topic; Microtubule-Associated Proteins - genetics; Non-synonymous SNP; Polymorphism, Single Nucleotide - genetics; Protein Tyrosine Phosphatases, Non-Receptor - genetics; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; PTPN21; Schizophrenia; Schizophrenia - genetics; Genetic association study; Data-mining; PTPN21; Non-synonymous SNP; Informatic prioritization; Psychosis; Human; Schizophrenia; Genetics; Data mining
• ISSN: 0920-9964; 1573-2509
• DOI: 10.1016/j.schres.2011.06.023

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 (r2 > 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.