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

The International schizophrenia consortium

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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.

Original languageEnglish (US)
Pages (from-to)43-51
Number of pages9
JournalSchizophrenia Research
Volume131
Issue number1-3
DOIs
StatePublished - Sep 1 2011

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Keywords

  • Data-mining
  • Genetic association study
  • Informatic prioritization
  • Non-synonymous snp
  • PTPN21

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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