Comprehensive search for Alzheimer disease susceptibility loci in the APOE region.

Archives of neurology Pub Date : 2012-10-01 DOI:10.1001/archneurol.2012.2052

Gyungah Jun, Badri N Vardarajan, Jacqueline Buros, Chang-En Yu, Michele V Hawk, Beth A Dombroski, Paul K Crane, Eric B Larson, Richard Mayeux, Jonathan L Haines, Kathryn L Lunetta, Margaret A Pericak-Vance, Gerard D Schellenberg, Lindsay A Farrer

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引用次数: 113

Abstract

Objective: To evaluate the association of risk and age at onset (AAO) of Alzheimer disease (AD) with single-nucleotide polymorphisms (SNPs) in the chromosome 19 region including apolipoprotein E (APOE) and a repeat-length polymorphism in TOMM40 (poly-T, rs10524523).

Design: Conditional logistic regression models and survival analysis.

Setting: Fifteen genome-wide association study data sets assembled by the Alzheimer's Disease Genetics Consortium.

Participants: Eleven thousand eight hundred forty AD cases and 10 931 cognitively normal elderly controls.

Main outcome measures: Association of AD risk and AAO with genotyped and imputed SNPs located in an 800-Mb region including APOE in the entire Alzheimer's Disease Genetics Consortium data set and with the TOMM40 poly-T marker genotyped in a subset of 1256 cases and 1605 controls.

Results: In models adjusting for APOE ε4, no SNPs in the entire region were significantly associated with AAO at P.001. Rs10524523 was not significantly associated with AD or AAO in models adjusting for APOE genotype or within the subset of ε3/ε3 subjects.

Conclusions: APOE alleles ε2, ε3, and ε4 account for essentially all the inherited risk of AD associated with this region. Other variants including a poly-T track in TOMM40 are not independent risk or AAO loci.

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APOE区域阿尔茨海默病易感位点的综合研究。

目的:评估阿尔茨海默病(AD)风险和发病年龄(AAO)与19号染色体区域载脂蛋白E (APOE)单核苷酸多态性(snp)和TOMM40重复长度多态性(poly-T, rs10524523)的关系。设计:条件逻辑回归模型和生存分析。背景:由阿尔茨海默病遗传学协会收集的15个全基因组关联研究数据集。参与者:11,840例AD病例和10,931例认知正常的老年人对照。主要结局指标:AD风险和AAO与位于800 mb区域的基因分型和估算snp的关联，包括整个阿尔茨海默病遗传学协会数据集中的APOE，以及1256例病例和1605例对照的TOMM40多聚t标记基因分型。结果:在调整APOE ε4的模型中，整个区域的snp与AAO均无显著相关性(p < 0.001)。在调整APOE基因型的模型中或在ε3/ε3受试者的子集中，Rs10524523与AD或AAO没有显著相关性。结论:APOE等位基因ε2、ε3和ε4是该区域AD遗传风险的主要原因。其他变异包括TOMM40的poly-T轨道不是独立的风险位点或AAO位点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Archives of neurology 医学-临床神经学

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