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

Jingchun Chen, Grace Lee, Ayman H Fanous, Zhongming Zhao, Peilin Jia, Anthony O'Neill, Dermot Walsh, Kenneth S Kendler, Xiangning Chen, International Schizophrenia Consortium, Francis O'Neill

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)43-51
Number of pages9
JournalSchizophrenia research
Volume131
Issue number1-3
DOIs
Publication statusPublished - Sep 2011

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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