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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: SCHIZOPHRENIA RESEARCH; v. 172, n. 1-3, p. 60-67, APR 2016.
• Citações Web of Science: 4

Resumo

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)

• Processo FAPESP: 13/13392-4 - Avaliação do uso dos análogos da crotamina em diagnóstico ou terapia
• Beneficiário: Mirian Akemi Furuie Hayashi
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/08941-6 - Estudo das oligopeptidases na esquizofrenia
• Beneficiário: Camila Miyagui Yonamine Asanuma
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 11/50740-5 - Prevenção na esquizofrenia e no transtorno bipolar da neurociência à comunidade: uma plataforma multifásica, multimodal e translacional para investigação e intervenção
• Beneficiário: Rodrigo Affonseca Bressan
• Modalidade de apoio: Auxílio à Pesquisa - Temático