Genome-wide investigation of schizophrenia associated plasma Ndel1 enzyme activity

详细信息    查看全文

• 作者：Ary Gadelha^a ; ^{aryararipe@yahoo.com.br" class="auth_mail" title="E-mail the corresponding author} ; ^{aryararipe@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Jonathan Coleman^b ; Gerome Breen^b ; ^h ; Diego Robles Mazzoti^c ; Camila M. Yonamine^a ; ^d ; Renata Pellegrino^e ; Vanessa Kiyomi Ota^a ; ^f ; Sintia Iole Belangero^a ; ^f ; Joseph Glessner^e ; Patrick Sleiman^e ; ^g ; Hakon Hakonarson^e ; ^g ; Mirian A.F. Hayashi^d ; ¹ ; ^{mhayashi@unifesp.br" class="auth_mail" title="E-mail the corresponding author} ; ^{mhayashi@yahoo.com" class="auth_mail" title="E-mail the corresponding author} ; Rodrigo A. Bressan^a ; ¹
• 关键词：SCZ ; schizophrenia ; HCs ; health controls ; GWAS ; Genome-Wide Association Studies ; Ndel1 ; Nuclear Distribution Element-Like 1 ; DISC1 ; Disrupted in Schizophrenia-1 ; SCID ; Structured clinical interview of DSM IV ; SNP ; Single Nucleotide Polymorphism ; BMI ; Body Mass Index ; CAMK1D ; Calcium/calmodulin-dependent protein kinase 1D ; MAGI2 ; Membrane-Associated Guanylate Kinase ; WW and PDZ Domains-Containing 2 ; GABRG3 ; Gamma-Aminobutyric Acid Receptor ; Gamma-3 ; CCDC25 ; Coiled-Coil Domain Containing Protein 2
• 刊名：Schizophrenia Research
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：172
• 期：1-3
• 页码：60-67
• 全文大小：672 K

文摘

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.