Association Analysis of Schizophrenia on 18 Genes Involved in Neuronal Migration: MDGA1 as a New Susceptibility Gene

被引：91

作者：

Kahler, Anna K. ^{[1
,2
,3
]}

Djurovic, Srdjan ^{[1
,2
,3
]}

Kulle, Bettina ^{[4
,5
]}

Jonsson, Erik G. ^{[6
]}

Agartz, Ingrid ^{[1
,6
,7
]}

Hall, Hakan ^{[6
]}

Opjordsmoen, Stein ^{[1
,3
]}

Jakobsen, Klaus D. ^{[8
]}

Hansen, Thomas ^{[8
]}

Melle, Ingrid ^{[1
,3
]}

Werge, Thomas ^{[8
]}

Steen, Vidar M. ^{[9
,10
]}

Andreassen, Ole A. ^{[1
,3
]}

机构：

[1] Univ Oslo, Inst Psychiat, TOP Project, Oslo, Norway

[2] Ullevaal Univ Hosp, Dept Med Genet, Oslo, Norway

[3] Ullevaal Univ Hosp, Dept Psychiat, N-0407 Oslo, Norway

[4] Univ Oslo, Dept Biostat, Oslo, Norway

[5] Univ Oslo, Dept Math, Oslo, Norway

[6] Karolinska Hosp & Inst, Psychiat Sect, HUBIN Project, Dept Clin Neurosci, Stockholm, Sweden

[7] Diakonhjemmet Hosp, Dept Psychiat Res, Oslo, Norway

[8] H S Sct Hans Hosp, Res Inst Biol Psychiat, Roskilde, Denmark

[9] Univ Bergen, Dept Clin Med, Dr Einar Martens Res Grp Biol Psychiat, Bergen, Norway

[10] Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway

来源：

AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS | 2008年 / 147B卷 / 07期

基金：

瑞典研究理事会; 英国医学研究理事会;

关键词：

neuron glia adhesion; radial neuron migration; association study; candidate gene; RELN;

D O I：

10.1002/ajmg.b.30726

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Several lines of evidence support the theory of schizophrenia (SZ) being a neurodevelopmental disorder. The structural, cytoarchitectural and functional brain abnormalities reported in patients with SZ, might be due to aberrant neuronal migration, since the final position of neurons affects neuronal function, morphology, and formation of synaptic connections. We have investigated the putative association between SZ and gene variants engaged in the neuronal migration process, by performing an association study on 839 cases and 1,473 controls of Scandinavian origin. Using a gene-wide approach, tagSNPs in 18 candidate genes have been genotyped, with gene products involved in the neuron-to-glial cell adhesion, interactions with the DISCI. protein and/or rearrangements of the cytoskeleton. Of the 289 markers tested, 19 markers located in genes MDGA1, RELN, ITGA3, DLX1, SPARCL1, and ASTN1, attained nominal significant P-values (P < 0.05) in either a genotypic or allelic association test. All of these genes, except transcription factor DLX1, are involved in the adhesion between neurons and radial glial cells. Eight markers obtained nominal significance in both tests, and were located in intronic or 3'UTR regions of adhesion molecule MDGA1 and previously reported SZ candidate RELN. The most significant result was attained for MDGA1 SNP rs9462341 (unadjusted association results: genotypic P = 0.00095; allelic P = 0.010). Several haplotypes within MDGA1, RELN, ITGA3, and ENAH were nominally significant. Further studies in independent samples are needed, including upcoming genome wide association study results, but our data suggest that MDGA1 is a new SZ susceptibility gene, and that altered neuronal migration is involved in SZ pathology. (C) 2008 Wiley-Liss, Inc.

引用

页码：1089 / 1100

页数：12