Neuregulin-1 polymorphism in late onset Alzheimer's disease families with psychoses
Neuregulin-1 polymorphism in late onset Alzheimer's disease families with psychoses
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DOI：
10.1002/ajmg.b.30219
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发表时间：
2005-11-05
影响因子：
2.8
通讯作者：
Sweet, RA
中科院分区：
文献类型：
--
作者：
Go, RCP;Perry, RT;Sweet, RA
患有晚发性阿尔茨海默病（LOAD）的先证者在30-60%的时间内表现出精神病的阳性症状。精神病的阳性症状已被证明在痴呆症发作之前出现，伴随着更大的认知缺陷，并预测更快的衰退。从NIMH阿尔茨海默氏病遗传倡议样本中的AD伴精神病（ADP）家族分布的研究表明，该性状是可遗传的，多重ADP家族的连锁研究发现2 p，6 q，8 p和21 q上的暗示性峰值。冰岛人群中特发性精神病，精神分裂症的基因组扫描在8 p12的神经调节蛋白-1（NRG 1）的5'区域内确定了一种风险单倍型。在苏格兰、爱尔兰和中国的其他精神分裂症人群中也发现了与NRG 1 SNP的关联。在这里，我们报告的结果表明，在NIMH AD数据集中，ADP在8 p12上有一个显着的连锁峰，包括NRG 1区域。我们还证明了NRGl SNP（单核苷酸多态性）rs392499与ADP存在显著关联，X-2 = 7.0，P = 0.008。这个相同的SNP是3-SNP单倍型的一部分，优先传递给具有这种表型的个体。我们的研究结果表明，NRG 1在增加LOAD家族中精神病阳性症状的遗传风险中发挥作用。(c)2005 Wiley-Liss，Inc.
Probands with late onset Alzheimer's disease (LOAD) exhibit positive symptoms of psychosis, 30-60% of the time. Positive symptoms of psychosis have been shown to appear prior to the onset of dementia to be accompanied by greater cognitive deficits, and to predict a more rapid decline. A study of the distribution of AD with psychosis (ADP) in families from the NIMH Alzheimer's Disease Genetic Initiative sample indicates that the trait is heritable, and linkage studies of multiplex ADP families have found suggestive peaks on 2p, 6q, 8p, and 21q. A genome scan of idiopathic psychosis, schizophrenia, in the Icelandic population identified a risk haplotype within the 5' region of neuregulin-1 (NRG1) on 8p12. Associations with NRG1 SNPs have also been found in other schizophrenia populations from Scotland, Ireland, and China. Here, we report results demonstrating a significant linkage peak for ADP on 8p12 in the NIMH AD dataset, encompassing the NRG1 region. We also demonstrate that there is a significant association with a NRGl SNP (single nucleotide polymorphism), rs392499, with ADP, X-2 = 7.0, P = 0.008. This same SNP is part of a 3-SNP haplotype preferentially transmitted to individuals with this phenotype. Our results suggest that NRG1 plays a role in increasing the genetic risk to positive symptoms of psychosis in a proportion of LOAD families. (c) 2005 Wiley-Liss, Inc.