title: Two non-synonymous markers in PTPN21, identified by genome-wide association study data-mining and replication, are associated with schizophrenia.
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.
authors.affiliation: Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Suite 390, 800 E. Leigh Street, Richmond, VA 23298, USA.
authors.forename: Jingchun
authors.initials: J
authors.lastname: Chen
authors.forename: Grace
authors.initials: G
authors.lastname: Lee
authors.forename: Ayman H
authors.initials: AH
authors.lastname: Fanous
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Zhao
authors.forename: Peilin
authors.initials: P
authors.lastname: Jia
authors.forename: Anthony
authors.initials: A
authors.lastname: O'Neill
authors.forename: Dermot
authors.initials: D
authors.lastname: Walsh
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kendler
authors.forename: Xiangning
authors.initials: X
authors.lastname: Chen
mesh_terms: D019295:Computational Biology / Q000379:methods / Q000706:statistics & numerical data; D030541:Databases, Genetic / Q000706:statistics & numerical data; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D015201:Meta-Analysis as Topic; D008869:Microtubule-Associated Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*
chemical_list: D008869:Microtubule-Associated Proteins; C409985:PTPN21 protein, human; D054558:Protein Tyrosine Phosphatases, Non-Receptor