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

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• 作者：Jessica E. van Schijndel ; Karen M.J. van Loo ; Martine van Zweeden ; Srdjan Djurovic ; Ole A. Andreassen ; Thomas Hansen ; Thomas Werge ; Pekka Kallunki ; Jan T. Pedersen ; Gerard J.M. Martens
• 关键词：Single-nucleotide polymorphism ; Case-control study ; Meta-analysis ; Development ; NTRK1 receptor
• 刊名：Journal of Psychiatric Research
• 出版年：2009
• 出版时间：October 2009
• 年：2009
• 卷：43
• 期：15
• 页码：1195-1199
• 全文大小：160 K

文摘

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.