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

Chen, J., Lee, G., Fanous, A. H., Zhao, Z., Jia, P., O'Neill, A., Walsh, D., Kendler, K. S., Chen, X., International Schizophrenia Consortium, , Craddock, Nicholas John, Georgieva, Lyudmila, Holmans, Peter Alan, Kirov, George, O'Donovan, Michael Conlon, Owen, Michael John, Ruderfer, Doug, Williams, Hywel and Williams, Nigel Melville 2011. Two non-synonymous markers in PTPN21, identified by genome-wide association study data-mining and replication, are associated with schizophrenia. Schizophrenia Research 131 (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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Systems Immunity Research Institute (SIURI)
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > R Medicine (General)
Additional Information: Nick Craddock, Lyudmila Georgieva, Peter Holmans, George Kirov, Michael O'Donovan, Michael Owen, Doug Rudefer, Hywel Williams and Nigel Williams are collaborators on this article.
Publisher: Elsevier B.V.
ISSN: 0920-9964
Last Modified: 21 Jun 2019 19:31
URI: http://orca-mwe.cf.ac.uk/id/eprint/80379

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