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, The International Schizophrenia Consortium (ISC), David St Clair

Research output: Contribution to journalArticle

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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 (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
Early online date14 Jul 2011
DOIs
Publication statusPublished - Sep 2011

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Data Mining
Genome-Wide Association Study
Schizophrenia
Linkage Disequilibrium
Haplotypes
Single Nucleotide Polymorphism
Meta-Analysis
Genes
Datasets

Keywords

  • computational biology
  • databases, genetic
  • gene frequency
  • genetic predisposition to disease
  • genome-wide association study
  • humans
  • linkage disequilibrium
  • meta-analysis as topic
  • microtubule-associated proteins
  • polymorphism, single nucleotide
  • protein tyrosine phosphatases, non-receptor
  • schizophrenia

Cite this

Two non-synonymous markers in PTPN21, identified by genome-wide association study data-mining and replication, are associated with schizophrenia. / 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 (ISC) ; St Clair, David.

In: Schizophrenia Research, Vol. 131, No. 1-3, 09.2011, p. 43-51.

Research output: Contribution to journalArticle

Chen, J, Lee, G, Fanous, AH, Zhao, Z, Jia, P, O'Neill, A, Walsh, D, Kendler, KS, Chen, X, The International Schizophrenia Consortium (ISC) & St Clair, D 2011, 'Two non-synonymous markers in PTPN21, identified by genome-wide association study data-mining and replication, are associated with schizophrenia', Schizophrenia Research, vol. 131, no. 1-3, pp. 43-51. https://doi.org/10.1016/j.schres.2011.06.023
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 (ISC) ; St Clair, David. / Two non-synonymous markers in PTPN21, identified by genome-wide association study data-mining and replication, are associated with schizophrenia. In: Schizophrenia Research. 2011 ; Vol. 131, No. 1-3. pp. 43-51.
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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 (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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T1 - Two non-synonymous markers in PTPN21, identified by genome-wide association study data-mining and replication, are associated with schizophrenia

AU - Chen, Jingchun

AU - Lee, Grace

AU - Fanous, Ayman H

AU - Zhao, Zhongming

AU - Jia, Peilin

AU - O'Neill, Anthony

AU - Walsh, Dermot

AU - Kendler, Kenneth S

AU - Chen, Xiangning

AU - The International Schizophrenia Consortium (ISC)

AU - St Clair, David

N1 - Published by Elsevier B.V.

PY - 2011/9

Y1 - 2011/9

N2 - 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.

AB - 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.

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KW - databases, genetic

KW - gene frequency

KW - genetic predisposition to disease

KW - genome-wide association study

KW - humans

KW - linkage disequilibrium

KW - meta-analysis as topic

KW - microtubule-associated proteins

KW - polymorphism, single nucleotide

KW - protein tyrosine phosphatases, non-receptor

KW - schizophrenia

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DO - 10.1016/j.schres.2011.06.023

M3 - Article

VL - 131

SP - 43

EP - 51

JO - Schizophrenia Research

JF - Schizophrenia Research

SN - 0920-9964

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