The number of trait loci in late-onset Alzheimer disease
The number of trait loci in late-onset Alzheimer disease
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DOI：
10.1086/302710
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发表时间：
2000-01-01
影响因子：
9.8
通讯作者：
Wijsman, EM
中科院分区：
文献类型：
--
作者：
Daw, EW;Payami, H;Wijsman, EM
虽然载脂蛋白e在晚发性阿尔茨海默病（AD）的遗传学中起重要作用是明确的，但有证据表明，其他基因可能在AD中起作用，并且对载脂蛋白e对AD发病差异的总贡献的估计差异很大。不幸的是，关于额外基因的数量和贡献的信息很少。我们对75个家族（742个个体）的迟发性阿尔茨海默病成员进行寡基因分离分析，估计了额外的数量性状位点的数量及其对阿尔茨海默病发病年龄差异的贡献，以及载脂蛋白e和性别的贡献。我们发现有证据表明，另外四个位点对晚发型AD发病年龄差异的贡献与载脂蛋白e相似或更大，其中一个位点的贡献是载脂蛋白e的几倍。此外，我们证实了先前的发现，apoE 4等位基因存在剂量效应，epsilon 2等位基因存在保护效应，apoE位点存在等位基因相互作用的证据，并且对男性有小的保护作用。此外，尽管我们估计载脂蛋白e基因型对阿尔茨海默病发病年龄的影响小于或等于17岁，但我们估计载脂蛋白e对阿尔茨海默病发病总变异的贡献（7%-9%）略小于之前报道的结果。我们的研究结果表明，一些尚未定位的基因可能在晚发性AD中发挥比apoE更大的作用。
Although it is clear that apoE plays an important role in the genetics of late-onset Alzheimer disease (AD), evidence exists that additional genes may play a role in AD, and estimates of the total contribution of apoE to the variance in onset of AD vary widely. Unfortunately, little information is available on the number and contribution of additional genes. We estimated the number of additional quantitative-trait loci and their contribution to the variance in age at onset of AD, as well as the contribution of apoE and sex, in an oligogenic segregation analysis of 75 families (742 individuals) ascertained for members with late-onset AD. We found evidence that four additional loci make a contribution to the variance in age at onset of late-onset AD that is similar to or greater in magnitude than that made by apoE, with one locus making a contribution several times greater than that of apoE. Additionally, we confirmed previous findings of a dose effect for the apoE epsilon 4 allele, a protective effect for the epsilon 2 allele, evidence for allelic interactions at the apoE locus, and a small protective effect for males. Furthermore, although we estimate that the apoE genotype can make a difference of less than or equal to 17 years in age at onset of AD, our estimate of the contribution of apoE (7%-9%) to total variation in onset of AD is somewhat smaller than that which has previously been reported. Our results suggest that several genes that have not yet been localized may play a larger role than does apoE in late-onset AD.