Ancestral origin of ApoE ε4 Alzheimer disease risk in Puerto Rican and African American populations
Ancestral origin of ApoE ε4 Alzheimer disease risk in Puerto Rican and African American populations
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DOI：
10.1371/journal.pgen.1007791
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发表时间：
2018-12-01
期刊：
影响因子：
4.5
通讯作者：
Pericak-Vance, Margaret A.
中科院分区：
文献类型：
--
作者：
Rajabli, Farid;Feliciano, Briseida E.;Pericak-Vance, Margaret A.
ApoE ε 4等位基因是迟发性阿尔茨海默病最重要的遗传危险因素。然而，epsilon - 4带来的风险因人群而异，与欧洲或亚洲血统的人群相比，非洲血统的人群显示出较低的epsilon - 4风险。造成这种风险效应异质性的原因目前尚不清楚；这可能是由于与祖先相关的环境或文化因素，也可能是由于ApoE区域的遗传变异在人群中有所不同。探索这些假设可能会导致新的、针对特定人群的治疗方法和风险预测。为了验证这些假设，我们分析了非裔美国人和波多黎各人个体的ApoE基因型和全基因组阵列数据。共有1766名患有晚发性阿尔茨海默病的非裔美国人和220名波多黎各人，以及3730名认知健康的非裔美国人和169名波多黎各人（年龄在65岁至65岁之间）参加了这项研究。我们首先评估了整个基因组的平均祖先（“全球”祖先），然后测试了它与ApoE基因型的相互作用。接下来，我们评估了ApoE等位基因的祖先背景（“本地”祖先），并测试了ApoE本地祖先是否影响阿尔茨海默病的风险，同时控制了全球祖先。全球祖先的测量显示与ApoE风险没有相互作用（波多黎各：p值= 0.49；非洲裔美国人：p值= 0.65）。相反，ApoE区域的本地祖先在两个人群中都显示出与ApoE ε 4等位基因的相互作用（波多黎各：p值= 0.019；非裔美国人：p值= 0.005）。非洲背景的ApoE ε 4等位基因比欧洲祖先背景的人具有更低的风险，无论人口如何（波多黎各人：非洲背景OR = 1.26，欧洲背景OR = 4.49；非洲裔美国人：非洲背景OR = 2.34，欧洲背景OR = 3.05）。导致ApoE基因epsilon 4等位基因风险效应较低的因素可能是由于ApoE附近的祖先特异性遗传因素，而不是非遗传的种族、文化和环境因素。
The ApoE epsilon 4 allele is the most significant genetic risk factor for late-onset Alzheimer disease. The risk conferred by epsilon 4, however, differs across populations, with populations of African ancestry showing lower epsilon 4 risk compared to those of European or Asian ancestry. The cause of this heterogeneity in risk effect is currently unknown; it may be due to environmental or cultural factors correlated with ancestry, or it may be due to genetic variation local to the ApoE region that differs among populations. Exploring these hypotheses may lead to novel, population-specific therapeutics and risk predictions. To test these hypotheses, we analyzed ApoE genotypes and genome-wide array data in individuals from African American and Puerto Rican populations. A total of 1,766 African American and 220 Puerto Rican individuals with late-onset Alzheimer disease, and 3,730 African American and 169 Puerto Rican cognitively healthy individuals (> 65 years) participated in the study. We first assessed average ancestry across the genome ("global" ancestry) and then tested it for interaction with ApoE genotypes. Next, we assessed the ancestral background of ApoE alleles ("local" ancestry) and tested if ancestry local to ApoE influenced Alzheimer disease risk while controlling for global ancestry. Measures of global ancestry showed no interaction with ApoE risk (Puerto Rican: p-value = 0.49; African American: p-value = 0.65). Conversely, ancestry local to the ApoE region showed an interaction with the ApoE epsilon 4 allele in both populations (Puerto Rican: p-value = 0.019; African American: p-value = 0.005). ApoE epsilon 4 alleles on an African background conferred a lower risk than those with a European ancestral background, regardless of population (Puerto Rican: OR = 1.26 on African background, OR = 4.49 on European; African American: OR = 2.34 on African background, OR = 3.05 on European background). Factors contributing to the lower risk effect in the ApoE gene epsilon 4 allele are likely due to ancestry-specific genetic factors near ApoE rather than non-genetic ethnic, cultural, and environmental factors.