Genome-wide investigation of schizophrenia associated plasma Ndel1 enzyme activity

Genome-wide investigation of schizophrenia associated plasma Ndel1 enzyme activity

Author Gadelha, Ary Autor UNIFESP Google Scholar
Coleman, Jonathan Google Scholar
Breen, Gerome Google Scholar
Mazzoti, Diego Robles Autor UNIFESP Google Scholar
Yonamine, Camila Miyagui Autor UNIFESP Google Scholar
Pellegrino, Renata Google Scholar
Ota, Vanessa Kiyomi Autor UNIFESP Google Scholar
Belangero, Sintia Iole Autor UNIFESP Google Scholar
Glessner, Joseph Google Scholar
Sleiman, Patrick Google Scholar
Hakonarson, Hakon Google Scholar
Hayashi, Mirian Akemi Furuie Autor UNIFESP Google Scholar
Bressan, Rodrigo Affonseca Autor UNIFESP Google Scholar
Abstract 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.
Keywords Ndel1
Enzyme activity
xmlui.dri2xhtml.METS-1.0.item-coverage Amsterdam
Language English
Sponsor Sao Paulo Research Foundation (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo - FAPESP)
National Council of Technological and Scientific Development (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico - CNPq)
Grant number FAPESP: 2011/50740-5
FAPESP: 2013/13392-4
FAPESP: 2009/51587-6
FAPESP: 2012/08941-6
CNPq: 477760/2010-4
CNPq: 557753/2010-4
CNPq: 508113/2010-5
CNPq: 311815/2012-0
CNPq: 475739/2013-2
Date 2016
Published in Schizophrenia Research. Amsterdam, v. 172, p. 60-67, 2016.
ISSN 0920-9964 (Sherpa/Romeo, impact factor)
Publisher Elsevier Science Bv
Extent 60-67
Access rights Closed access
Type Article
Web of Science ID WOS:000373528100010

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