Support for NRG1 as a Susceptibility Factor for Schizophrenia in a Northern Swedish Isolated Population
Support for NRG1 as a Susceptibility Factor for Schizophrenia in a Northern Swedish Isolated Population
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DOI：
10.1001/archgenpsychiatry.2009.82
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发表时间：
2009-08-01
影响因子：
--
通讯作者：
Del-Favero, Jurgen
中科院分区：
文献类型：
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作者：
Alaerts, Maaike;Ceulemans, Shana;Del-Favero, Jurgen
内容：神经调节蛋白1（NRG 1）是一种参与神经发育、髓鞘形成、神经递质受体表达和突触可塑性的生长因子，当该基因5'端的7标记单倍型（Hap（ICE））被证明与冰岛人群中的精神分裂症相关时，它首次加入了精神分裂症候选基因的名单。从那时起，更多的遗传和功能的证据已经出现，这支持了NRG 1在精神分裂症的发展中的作用。目的：确定NRG 1的贡献精神分裂症的易感性在北方Swedish isolated population.Design：详细的连锁不平衡（LD）为基础的患者-对照关联研究。这是第一项对7个Hap（ICE）标记和一组32个HapMap标记单核苷酸多态性（SNP）进行分型和分析的研究，这些SNP代表了次要等位基因频率至少为1%的变异，并充分表征了NRG 1 5'部分的LD结构。从瑞典北方隔离人群中招募了486名无关的精神分裂症患者和514名无关的对照个体。Hap（ICE）标记的分析表明，7-标记和2-微卫星单倍型的关联，与冰岛人群中相关的单倍型不同，并在瑞典北方对照个体中过度表达。随后，通过研究单倍型关联，依赖和独立于LD块结构，进行了包括所有37个基因型SNP的更详细的分析。我们发现位于NRG 1第二内含子的5个SNPs（.007
Context: Neuregulin 1 (NRG1), a growth factor involved in neurodevelopment, myelination, neurotransmitter receptor expression, and synaptic plasticity, first joined the list of candidate genes for schizophrenia when a 7-marker haplotype at the 5' end of the gene (Hap(ICE)) was shown to be associated with the disorder in the Icelandic population. Since then, more genetic and functional evidence has emerged, which supports a role for NRG1 in the development of schizophrenia.Objective: To determine the contribution of NRG1 to susceptibility for schizophrenia in a northern Swedish isolated population.Design: Detailed linkage disequilibrium (LD)-based patient- control association study. This is the first study to type and analyze the 7 Hap(ICE) markers and a set of 32 HapMap tagging single-nucleotide polymorphisms (SNPs) that represents variants with a minor allele frequency of at least 1% and fully characterizes the LD structure of the 5' part of NRG1.Setting: Outpatient and inpatient hospitals.Participants: A total of 486 unrelated patients with schizophrenia and 514 unrelated control individuals recruited from a northern Swedish isolated population.Main Outcome Measures: Association between markers and disease.Results: Analysis of the Hap(ICE) markers showed the association of a 7-marker and 2-microsatellite haplotype, different from the haplotypes associated in the Icelandic population and overrepresented in northern Swedish control individuals. Subsequently, a more detailed analysis that included all 37 genotyped SNPs was performed by investigating haplotypic association, dependent and independent of LD block structure. We found significant association with 5 SNPs located in the second intron of NRG1 (.007