GAB2 as an Alzheimer disease susceptibility gene: follow-up of genomewide association results.
GAB2 as an Alzheimer disease susceptibility gene: follow-up of genomewide association results.
复制标题
DOI：
10.1001/archneurol.2008.552
复制
发表时间：
2009-02
影响因子：
--
通讯作者：
Bertram, Lars
中科院分区：
文献类型：
--
作者：
Schjeide, Brit-Maren M.;Hooli, Basavaraj;Parkinson, Michele;Hogan, Meghan F.;DiVito, Jason;Mullin, Kristina;Blacker, Deborah;Tanzi, Rudolph E.;Bertram, Lars
全基因组关联（GWA）研究最近发现了4个新的阿尔茨海默病（AD）易感位点（GAB2、GOLM1和迄今为止染色体9p和15q上的2个未表征的位点）。据我们所知，这些发现还没有被独立地重复。在4个受AD影响家庭的大型数据集中评估GWA的发现。对先前研究中遗传关联发现的随访。学术研究。来自近1300个AD患者家庭的4000多个DNA样本。采用基于家族的方法对4个GWA信号rs7101429 [GAB2]、rs7019241 [GOLM1]、rs10519262[染色体15q]和rs9886784[染色体9p]进行遗传关联分析测试。在综合分析中，GAB2中只有rs7101429与原始GWA研究中的相同等位基因存在显著关联（P = 0.002）。这一结果与最近对GAB2多态性的荟萃分析一致，表明携带少量等位基因的人患AD的风险降低了约30%。在调查的数据集中，其他3个测试的基因座均未显示出与AD相关的一致证据。GAB2包含可能导致AD风险适度变化的遗传变异。尽管有这些令人鼓舞的结果，但需要更多来自独立样本的数据来更好地评估GAB2对普通人群AD风险的潜在贡献。
Genomewide association (GWA) studies have recently implicated 4 novel Alzheimer disease (AD) susceptibility loci (GAB2, GOLM1, and 2 uncharacterized loci to date on chromosomes 9p and 15q). To our knowledge, these findings have not been independently replicated. To assess these GWA findings in 4 large data sets of families affected by AD. Follow-up of genetic association findings in previous studies. Academic research. More than 4000 DNA samples from almost 1300 families affected with AD. Genetic association analysis testing of 4 GWA signals (rs7101429 [GAB2], rs7019241 [GOLM1], rs10519262 [chromosome 15q], and rs9886784 [chromosome 9p]) using family-based methods. In the combined analyses, only rs7101429 in GAB2 yielded significant evidence of association with the same allele as in the original GWA study (P = .002). The results are in agreement with recent meta-analyses of this and other GAB2 polymorphisms suggesting approximately a 30% decrease in risk for AD among carriers of the minor alleles. None of the other 3 tested loci showed consistent evidence for association with AD across the investigated data sets. GAB2 contains genetic variants that may lead to a modest change in the risk for AD. Despite these promising results, more data from independent samples are needed to better evaluate the potential contribution of GAB2 to AD risk in the general population.
登录
查看更多内容
影响因子：
4.8
作者：
Nizzari, Mario;Venezia, Valentina;Russo, Claudio
通讯作者：
Russo, Claudio
DOI：
10.1073/pnas.90.5.1977
发表时间：
1993-03-01
影响因子：
11.1
作者：
STRITTMATTER, WJ;SAUNDERS, AM;ROSES, AD
通讯作者：
ROSES, AD
影响因子：
--
作者：
Li, Hao;Wetten, Sally;Roses, Allen D.
通讯作者：
Roses, Allen D.
影响因子：
158.5
作者：
Bertram, L;Hiltunen, M;Tanzi, RE
通讯作者：
Tanzi, RE
影响因子：
9.9
作者：
SAUNDERS, AM;STRITTMATTER, WJ;ROSES, AD
通讯作者：
ROSES, AD