SORL1 is genetically associated with neuropathologically characterized late-onset Alzheimer's disease.
SORL1 is genetically associated with neuropathologically characterized late-onset Alzheimer's disease.
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DOI：
10.3233/jad-122395
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发表时间：
2013
期刊：
影响因子：
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通讯作者：
Yanan Wen;A. Miyashita;N. Kitamura;Tamao Tsukie;Yuko Saito;H. Hatsuta;S. Murayama;A. Kakita;
中科院分区：
文献类型：
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作者：
Yanan Wen;A. Miyashita;N. Kitamura;Tamao Tsukie;Yuko Saito;H. Hatsuta;S. Murayama;A. Kakita;
在一项涉及临床验证受试者的大规模全基因组关联研究（GWAS）中，SORL 1被证明与迟发性阿尔茨海默病（LOAD）遗传相关。在这里，我们试图通过涉及19个SNP的基于单核苷酸多态性（SNP）的遗传研究在日本神经病理学特征的脑供体受试者（LOAD，213;对照，370）中复制SORL 1的相关性：11个SNP选自Rogaeva等人（2007）报告的初始研究，其他8个来自我们的GWAS。在这些SNPs中，经多重检验校正后，5个SNPs与LOAD显著相关（p <2.63 E-03 [ = 0.05/19]），这得到了调整年龄、性别和APOE ε4等位基因携带状态的多元logistic回归分析的支持。这些SNP中的三个（rs 985421、rs 12364988 [Rogaeva的SNP 7]和rs 4598682）由5'连锁不平衡（LD）区域涵盖，并且其余两个（rs3781834和rs3781836）由3' LD区域涵盖。在每个LD区域内观察到SNP之间的强LD，这意味着有两个基因组区域显示与SORL 1中的LOAD相关。病例对照单倍型分析表明，一些单倍型与两个LD区域的LOAD相关。我们的复制研究有力地支持了先前的证据，SORL 1可能是与LOAD相关的基因之一。
SORL1 was shown to be genetically associated with late-onset Alzheimer's disease (LOAD) in a large-scale genome-wide association study (GWAS) involving clinically verified subjects. Here, we attempted to replicate the association of SORL1 in Japanese neuropathologically characterized brain donor subjects (LOAD, 213; control, 370) through a single-nucleotide polymorphism (SNP)-based genetic study involving 19 SNPs: 11 SNPs were selected from the initial study reported by Rogaeva et al. (2007), and the other eight were from our GWAS. Among these SNPs, five exhibited a significant association with LOAD after multiple test correction (p < 2.63E-03 [ = 0.05/19]), which was supported by means of multiple logistic regression analysis with adjustment for age, gender, and carrier status of the APOE ε4 allele. Three of these SNPs (rs985421, rs12364988 [Rogaeva's SNP 7], and rs4598682) were encompassed by a 5' linkage disequilibrium (LD) region, and the remaining two (rs3781834 and rs3781836) by a 3' LD region. Strong LD among SNPs was observed within each LD region, implying that there are two genomic regions showing association with LOAD in SORL1. Case-control haplotype analysis demonstrated that some haplotypes are associated with LOAD in both LD regions. Our replication study strongly supports the preceding evidence that SORL1 is likely one of the genes associated with LOAD.