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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Genome-wide investigation of schizophrenia associated plasma Ndel1 enzyme activity

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Gadelha, Ary [1] ; Coleman, Jonathan [2] ; Breen, Gerome [3, 2, 4] ; Mazzoti, Diego Robles [5] ; Yonamine, Camila M. [1, 6] ; Pellegrino, Renata [7] ; Ota, Vanessa Kiyomi [1, 8] ; Belangero, Sintia Iole [1, 8] ; Glessner, Joseph [7] ; Sleiman, Patrick [7, 9] ; Hakonarson, Hakon [7, 9] ; Hayashi, Mirian A. F. [6] ; Bressan, Rodrigo A. [1]
Total Authors: 13
[1] Univ Fed Sao Paulo UNIFESP EPM, Dept Psychiat, Ed Pesquisas 2, Rua Pedro de Toledo 669, 3rd Floor, BR-04039032 Sao Paulo, SP - Brazil
[2] Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC, Social Genet & Dev Psychiat Ctr, London WC2R 2LS - England
[3] Kings Coll London, Inst Psychiat Psychol & Neurosci, London WC2R 2LS - England
[4] Kings Coll London, Maudsley Hosp, Natl Inst Hlth Res, Biomed Res Ctr Mental Hlth, London WC2R 2LS - England
[5] UNIFESP EPM, Dept Psychobiol, Sao Paulo - Brazil
[6] UNIFESP EPM, Dept Pharmacol, Sao Paulo - Brazil
[7] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 - USA
[8] UNIFESP EPM, Dept Morphol & Genet, Sao Paulo - Brazil
[9] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 - USA
Total Affiliations: 9
Document type: Journal article
Source: SCHIZOPHRENIA RESEARCH; v. 172, n. 1-3, p. 60-67, APR 2016.
Web of Science Citations: 4

Ndel1 is a DISC1-interacting oligopeptidase that cleaves in vitro neuropeptides as neurotensin and bradykinin, and which has been associated with both neuronal migration and neurite outgrowth. We previously reported that plasma Ndel1 enzyme activity is lower in patients with schizophrenia (SCZ) compared to healthy controls (HCs). To our knowledge, no previous study has investigated the genetic factors associated with the plasma Ndel1 enzyme activity. In the current analyses, samples from 83 SCZ patients and 92 control subjects that were assayed for plasma Ndel1 enzyme activity were genotyped on Illumina Omni Express arrays. A genetic relationship matrix using genome-wide information was then used for ancestry correction, and association statistics were calculated genome-wide. Ndel1 enzyme activity was significantly lower in patients with SCZ (t=4.9; p < 0.001) and was found to be associated with CAMK1D, MAGI2, CCDC25, and GABGR3, at a level of suggestive significance (p < 10(-6)), independent of the clinical status. Then, we performed a model to investigate the observed differences for case/control measures. 2 SNPs at region 1p22.2 reached the p < 10(-7) level. ZFPM2 and MAD1L1 were the only two genes with more than one hit at 10-6 order of p value. Therefore, Ndel1 enzyme activity is a complex trait influenced by many different genetic variants that may contribute to SCZ physiopathology. (C) 2016 Elsevier B.V. All rights reserved. (AU)

FAPESP's process: 13/13392-4 - Evaluation of the use of analogs of crotamine for diagnosis or therapy
Grantee:Mirian Akemi Furuie Hayashi
Support Opportunities: Regular Research Grants
FAPESP's process: 12/08941-6 - The study of oligopeptidases in schizophrenia
Grantee:Camila Miyagui Yonamine Asanuma
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 11/50740-5 - Prevention in schizophrenia and bipolar disorder from neuroscience to the community: a multiphase, multimodal and translational platform for research and intervention
Grantee:Rodrigo Affonseca Bressan
Support Opportunities: Research Projects - Thematic Grants