OBJECTIVE: Striatal-enriched protein tyrosine phosphatase (STEP) is a brain-specific member of the protein tyrosine phosphatase (PTP) family that has been implicated in learning and memory. In this study, we examined the association of the protein tyrosine phosphatase non-receptor 5 (PTPN5) gene, which encodes for STEP, with both schizophrenia and cognitive functioning in the Israeli Jewish population. METHODS: A schizophrenia (SZ) case-control study of 868 participants was carried out (286 patients and 582 controls). Eleven PTPN5 tagging single-nucleotide polymorphisms (SNPs) were selected and single markers and haplotype association analyses were carried out. A cognitive variability study included 437 healthy women who completed a computerized cognitive battery. We performed univariate associations between the SNPs and cognitive performance. The possible functional role of these variants was examined by studying their association with gene expression levels in the brain. RESULTS: In the SZ study, we found a nominal association in the whole sample between rs4075664 and SZ. Male patients with SZ showed a more significant association for three SNPs (rs4075664, rs2278732, and rs4757710). Haplotypes of the studied SNPs were associated with SZ both in the overall sample and within the male subsample. Expression analysis provided some support for the effects of the associated SNPs on PTPN5 expression level. The cognitive variability study showed positive associations between PTPN5 SNPs and different cognitive subtests. Principal component analysis showed an 'attention index' neurocognitive component that was associated with two SNP pairs (rs10832983 × rs10766504 and rs7932938 × rs4757718). CONCLUSION: The results imply a model in which PTPN5 may play a role in normal cognitive functioning and contribute to aspects of the neuropathology of SZ.
OBJECTIVE:Striatal-enriched protein tyrosine phosphatase (STEP) is a brain-specific member of the protein tyrosine phosphatase (PTP) family that has been implicated in learning and memory. In this study, we examined the association of the protein tyrosine phosphatase non-receptor 5 (PTPN5) gene, which encodes for STEP, with both schizophrenia and cognitive functioning in the Israeli Jewish population. METHODS: A schizophrenia (SZ) case-control study of 868 participants was carried out (286 patients and 582 controls). Eleven PTPN5 tagging single-nucleotide polymorphisms (SNPs) were selected and single markers and haplotype association analyses were carried out. A cognitive variability study included 437 healthy women who completed a computerized cognitive battery. We performed univariate associations between the SNPs and cognitive performance. The possible functional role of these variants was examined by studying their association with gene expression levels in the brain. RESULTS: In the SZ study, we found a nominal association in the whole sample between rs4075664 and SZ. Male patients with SZ showed a more significant association for three SNPs (rs4075664, rs2278732, and rs4757710). Haplotypes of the studied SNPs were associated with SZ both in the overall sample and within the male subsample. Expression analysis provided some support for the effects of the associated SNPs on PTPN5 expression level. The cognitive variability study showed positive associations between PTPN5 SNPs and different cognitive subtests. Principal component analysis showed an 'attention index' neurocognitive component that was associated with two SNP pairs (rs10832983 × rs10766504 and rs7932938 × rs4757718). CONCLUSION: The results imply a model in which PTPN5 may play a role in normal cognitive functioning and contribute to aspects of the neuropathology of SZ.
Authors: Jianxin Shi; Douglas F Levinson; Jubao Duan; Alan R Sanders; Yonglan Zheng; Itsik Pe'er; Frank Dudbridge; Peter A Holmans; Alice S Whittemore; Bryan J Mowry; Ann Olincy; Farooq Amin; C Robert Cloninger; Jeremy M Silverman; Nancy G Buccola; William F Byerley; Donald W Black; Raymond R Crowe; Jorge R Oksenberg; Daniel B Mirel; Kenneth S Kendler; Robert Freedman; Pablo V Gejman Journal: Nature Date: 2009-07-01 Impact factor: 49.962
Authors: Shane E McCarthy; Vladimir Makarov; George Kirov; Anjene M Addington; Jon McClellan; Seungtai Yoon; Diana O Perkins; Diane E Dickel; Mary Kusenda; Olga Krastoshevsky; Verena Krause; Ravinesh A Kumar; Detelina Grozeva; Dheeraj Malhotra; Tom Walsh; Elaine H Zackai; Paige Kaplan; Jaya Ganesh; Ian D Krantz; Nancy B Spinner; Patricia Roccanova; Abhishek Bhandari; Kevin Pavon; B Lakshmi; Anthony Leotta; Jude Kendall; Yoon-Ha Lee; Vladimir Vacic; Sydney Gary; Lilia M Iakoucheva; Timothy J Crow; Susan L Christian; Jeffrey A Lieberman; T Scott Stroup; Terho Lehtimäki; Kaija Puura; Chad Haldeman-Englert; Justin Pearl; Meredith Goodell; Virginia L Willour; Pamela Derosse; Jo Steele; Layla Kassem; Jessica Wolff; Nisha Chitkara; Francis J McMahon; Anil K Malhotra; James B Potash; Thomas G Schulze; Markus M Nöthen; Sven Cichon; Marcella Rietschel; Ellen Leibenluft; Vlad Kustanovich; Clara M Lajonchere; James S Sutcliffe; David Skuse; Michael Gill; Louise Gallagher; Nancy R Mendell; Nick Craddock; Michael J Owen; Michael C O'Donovan; Tamim H Shaikh; Ezra Susser; Lynn E Delisi; Patrick F Sullivan; Curtis K Deutsch; Judith Rapoport; Deborah L Levy; Mary-Claire King; Jonathan Sebat Journal: Nat Genet Date: 2009-10-25 Impact factor: 38.330
Authors: Shaun M Purcell; Naomi R Wray; Jennifer L Stone; Peter M Visscher; Michael C O'Donovan; Patrick F Sullivan; Pamela Sklar Journal: Nature Date: 2009-07-01 Impact factor: 49.962
Authors: Hreinn Stefansson; Roel A Ophoff; Stacy Steinberg; Ole A Andreassen; Sven Cichon; Dan Rujescu; Thomas Werge; Olli P H Pietiläinen; Ole Mors; Preben B Mortensen; Engilbert Sigurdsson; Omar Gustafsson; Mette Nyegaard; Annamari Tuulio-Henriksson; Andres Ingason; Thomas Hansen; Jaana Suvisaari; Jouko Lonnqvist; Tiina Paunio; Anders D Børglum; Annette Hartmann; Anders Fink-Jensen; Merete Nordentoft; David Hougaard; Bent Norgaard-Pedersen; Yvonne Böttcher; Jes Olesen; René Breuer; Hans-Jürgen Möller; Ina Giegling; Henrik B Rasmussen; Sally Timm; Manuel Mattheisen; István Bitter; János M Réthelyi; Brynja B Magnusdottir; Thordur Sigmundsson; Pall Olason; Gisli Masson; Jeffrey R Gulcher; Magnus Haraldsson; Ragnheidur Fossdal; Thorgeir E Thorgeirsson; Unnur Thorsteinsdottir; Mirella Ruggeri; Sarah Tosato; Barbara Franke; Eric Strengman; Lambertus A Kiemeney; Ingrid Melle; Srdjan Djurovic; Lilia Abramova; Vasily Kaleda; Julio Sanjuan; Rosa de Frutos; Elvira Bramon; Evangelos Vassos; Gillian Fraser; Ulrich Ettinger; Marco Picchioni; Nicholas Walker; Timi Toulopoulou; Anna C Need; Dongliang Ge; Joeng Lim Yoon; Kevin V Shianna; Nelson B Freimer; Rita M Cantor; Robin Murray; Augustine Kong; Vera Golimbet; Angel Carracedo; Celso Arango; Javier Costas; Erik G Jönsson; Lars Terenius; Ingrid Agartz; Hannes Petursson; Markus M Nöthen; Marcella Rietschel; Paul M Matthews; Pierandrea Muglia; Leena Peltonen; David St Clair; David B Goldstein; Kari Stefansson; David A Collier Journal: Nature Date: 2009-07-01 Impact factor: 49.962
Authors: Jian Xu; Pradeep Kurup; Tyler D Baguley; Ethan Foscue; Jonathan A Ellman; Angus C Nairn; Paul J Lombroso Journal: Cell Mol Life Sci Date: 2015-10-08 Impact factor: 9.261