Three-cohort targeted gene screening reveals a non-synonymous TRKA polymorphism associated with schizophrenia

被引：26

作者：

van Schijndel, Jessica E. ^{[1
]}

van Loo, Karen M. J. ^{[1
]}

van Zweeden, Martine ^{[1
]}

Djurovic, Srdjan ^{[2
,3
,4
]}

Andreassen, Ole A. ^{[2
,3
,4
]}

Hansen, Thomas ^{[5
]}

Werge, Thomas ^{[5
]}

Kallunki, Pekka ^{[6
]}

Pedersen, Jan T. ^{[6
]}

Martens, Gerard J. M. ^{[1
]}

机构：

[1] Radboud Univ Nijmegen, Dept Mol Anim Physiol, Donders Inst Brain Cognit & Behav, Fac Sci,NCMLS RT282, NL-6525 GA Nijmegen, Netherlands

[2] Univ Oslo, Inst Psychiat, N-0316 Oslo, Norway

[3] Ullevaal Univ Hosp, Dept Med Genet, N-0316 Oslo, Norway

[4] Ullevaal Univ Hosp, Dept Psychiat, N-0316 Oslo, Norway

[5] Copenhagen Univ Hosp, Res Inst Biol Psychiat, Mental Hlth Ctr Sct Hans, DK-4000 Roskilde, Denmark

[6] H Lundbeck & Co AS, DK-2500 Copenhagen, Denmark

来源：

JOURNAL OF PSYCHIATRIC RESEARCH | 2009年 / 43卷 / 15期

关键词：

Single-nucleotide polymorphism; Case-control study; Meta-analysis; Development; NTRK1; receptor; NEUREGULIN-1; GENE; METAANALYSIS; REELIN; PATHOGENESIS; EXPRESSION; RECEPTORS; LOCUS;

D O I：

10.1016/j.jpsychires.2009.04.006

中图分类号：

R749 [精神病学];

学科分类号：

100205 ;

摘要：

Schizophrenia is a complex neurodevelopmental disorder that is thought to be induced by an interaction between predisposing genes and environmental stressors. To identify predisposing genetic factors, we performed a targeted (mostly neurodevelopmental) gene approach involving the screening of 396 selected non-synonymous single-nucleotide polymorphisms (SNPs) in three independent Caucasian schizophrenia case-control cohorts (USA, Denmark and Norway). A meta-analysis revealed ten non-synonymous SNPs that were nominally associated with schizophrenia, nine of which have not been previously linked to the disorder. Risk alleles are in TRKA (rs6336), BARD1 (rs28997576), LAMA5 (rs3810548), DKK2 (rs7037102), NOD2 (rs2066844) and RELN (rs2229860), whereas protective alleles are in NOD2 (rs2066845), NRG1 (rs10503929), ADAM7 (rs13259668) and TNR (rs859427). Following correction for multiple testing, the most attractive candidate for further study concerns SNP rs6336 (q = 0.12) that causes the substitution of an evolutionarily highly conserved amino acid residue in the kinase domain of the neurodevelopmentally important receptor TRKA. Thus, TRKA signaling may represent a novel susceptibility pathway for schizophrenia. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：1195 / 1199

页数：5

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