Genetic Stratification to Identify Risk Groups for Alzheimer's Disease.
Genetic Stratification to Identify Risk Groups for Alzheimer's Disease.
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DOI：
10.3233/jad-161070
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Deary IJ
中科院分区：
文献类型：
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作者：
Marioni RE;Campbell A;Hagenaars SP;Nagy R;Amador C;Hayward C;Porteous DJ;Visscher PM;Deary IJ
阿尔茨海默病（AD）的遗传风险因素分层可能有助于确定疾病风险最大的群体。导致迟发性阿尔茨海默病的生物学变化很可能发生在诊断前几年，甚至几十年前。在这里，我们选择了苏格兰一代：苏格兰家庭健康研究队列的一个子集，其临床前年龄范围可能为60-70岁（子集n = 3,495，具有认知和遗传数据）。我们通过AD的多基因风险评分来测试认知差异。多基因评分使用所有可用的snp构建，不包括距离APOE位点500 kb以内的snp。APOE状态对这些关联的加性和乘法效应进行了研究。阿尔茨海默病多基因风险评分较高的患者的记忆力下降幅度较小（标准化β -0.04, p = 0.020）。这些关联与APOE状态无关。APOE单倍型的AD多基因得分无差异（p = 0.72）。AD多基因风险得分高的个体（分布的前5%和后5%）表现出认知能力的下降，尽管比APOE的个体要小得多（在处理速度测试中减少2.3分比3.5分，在记忆测试中减少1.8分比2.8分）。AD的多基因风险评分可以帮助识别认知能力下降和临床前AD风险最大的老年人。
Stratification by genetic risk factors for Alzheimer’s disease (AD) may help identify groups with the greatest disease risk. Biological changes that cause late-onset AD are likely to occur years, if not decades prior to diagnosis. Here, we select a subset of the Generation Scotland: Scottish Family Health Study cohort in a likely preclinical age-range of 60–70 years (subset n = 3,495 with cognitive and genetic data). We test for cognitive differences by polygenic risk scores for AD. The polygenic scores are constructed using all available SNPs, excluding those within a 500 kb distance of the APOE locus. Additive and multiplicative effects of APOE status on these associations are investigated. Small memory decrements were observed in those with high polygenic risk scores for AD (standardized beta –0.04, p = 0.020). These associations were independent of APOE status. There was no difference in AD polygenic scores across APOE haplotypes (p = 0.72). Individuals with high compared to low polygenic risk scores for AD (top and bottom 5% of the distribution) show cognitive decrements, albeit much smaller than for APOE ɛ4ɛ4 compared to ɛ3ɛ3 individuals (2.3 versus 3.5 fewer points on the processing speed test, and 1.8 versus 2.8 fewer points on the memory test). Polygenic risk scores for AD may help identify older individuals at greatest risk of cognitive decline and preclinical AD.