在瑞典北部一个隔离人群中，神经调节蛋白1作为精神分裂症易感性因素的证据支持。
Support for NRG1 as a susceptibility factor for schizophrenia in a northern Swedish isolated population.
作者信息
Alaerts Maaike, Ceulemans Shana, Forero Diego, Moens Lotte N, De Zutter Sonia, Heyrman Lien, Lenaerts An-Sofie, Norrback Karl-Fredrik, De Rijk Peter, Nilsson Lars-Göran, Goossens Dirk, Adolfsson Rolf, Del-Favero Jurgen
机构信息
Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology, University of Antwerp, B-2610 Antwerp, Belgium.
出版信息
Arch Gen Psychiatry. 2009 Aug;66(8):828-37. doi: 10.1001/archgenpsychiatry.2009.82.
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 </= P </= .04). Also, 2-, 3-, and 4-SNP windows that comprise these SNPs were associated (P < 3 x 10(-4)). One protective haplotype (0% vs 1.8%; P <5 x 10(-5)) and 1 disease risk-causing haplotype (40.4% vs 34.9%, P = .02) were defined.
CONCLUSION
The NRG1 gene contributes to the susceptibility for schizophrenia in the northern Swedish population.
背景
神经调节蛋白1（NRG1）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'端的一个7标记单倍型（Hap(ICE)）在冰岛人群中被证明与精神分裂症相关时，它首次进入了精神分裂症候选基因列表。从那时起，出现了更多的遗传和功能证据，支持NRG1在精神分裂症发病中的作用。
目的
确定NRG1对瑞典北部隔离人群精神分裂症易感性的影响。
设计
基于详细连锁不平衡（LD）的病例对照关联研究。这是第一项对7个Hap(ICE)标记以及一组32个HapMap标签单核苷酸多态性（SNP）进行分型和分析的研究，这些SNP代表次要等位基因频率至少为1%的变体，并全面表征了NRG1 5'部分区域的LD结构。
地点
门诊和住院医院。
参与者
从瑞典北部隔离人群中招募的486名无亲缘关系的精神分裂症患者和514名无亲缘关系的对照个体。
主要观察指标
标记与疾病之间的关联。
结果
对Hap(ICE)标记的分析显示，一种7标记和2微卫星单倍型存在关联，该单倍型不同于冰岛人群中相关的单倍型，在瑞典北部对照个体中过度出现。随后，通过研究单倍型关联（依赖和独立于LD块结构），对包括所有37个基因分型SNP在内的更详细分析进行了研究。我们发现与位于NRG1第二个内含子中的5个SNP存在显著关联（0.007 ≤ P ≤ 0.04）。此外，包含这些SNP的2、3和4个SNP窗口也存在关联（P < 3 × 10⁻⁴）。定义了一种保护性单倍型（0%对1.8%；P < 5 × 10⁻⁵）和一种疾病风险单倍型（40.4%对34.9%，P = 0.02）。
结论
NRG1基因对瑞典北部人群精神分裂症的易感性有影响。
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