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

The International schizophrenia consortium

Research output: Contribution to journalArticle

13 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 (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
Externally publishedYes

Fingerprint

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

Keywords

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

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

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

In: Schizophrenia Research, Vol. 131, No. 1-3, 01.09.2011, p. 43-51.

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 (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.",
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AU - The International schizophrenia consortium

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 - O’Donovan, Michael C.

AU - Kirov, George K.

AU - Craddock, Nick J.

AU - Holmans, Peter A.

AU - Williams, Nigel M.

AU - Georgieva, Lyudmila

AU - Nikolov, Ivan

AU - Norton, N.

AU - Norton, Nadine

AU - Toncheva, Draga

AU - Milanova, Vihra

AU - Owen, Michael J.

AU - Hultman, Christina M.

AU - Lichtenstein, Paul

AU - Thelander, Emma F.

AU - Sullivan, Patrick

AU - Morris, Derek W.

AU - O’Dushlaine, Colm T.

AU - Kenny, Elaine

AU - Quinn, Emma M.

AU - Gill, Michael

AU - Corvin, Aiden

AU - McQuillin, Andrew

AU - Choudhury, Khalid

AU - Datta, Susmita

AU - Pimm, Jonathan

AU - Thirumalai, Srinivasa

AU - Puri, Vinay

AU - Krasucki, Robert

AU - Lawrence, Jacob

AU - Quested, Digby

AU - Bass, Nicholas

AU - Gurling, Hugh

AU - Crombie, Caroline

AU - Fraser, Gillian

AU - Kuan, Soh Leh

AU - Walker, Nicholas

AU - St Clair, David

AU - Blackwood, Douglas H.R.

AU - Muir, Walter J.

AU - McGhee, Kevin A.

PY - 2011/9/1

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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 (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.

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 (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.

KW - Data-mining

KW - Genetic association study

KW - Informatic prioritization

KW - Non-synonymous snp

KW - PTPN21

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