孟德尔随机化
痴呆
载脂蛋白E
观察研究
一致性
人口
等位基因
内科学
阿尔茨海默病
医学
心理学
疾病
老年学
遗传学
生物
基因型
遗传变异
基因
环境卫生
作者
Katrine Laura Rasmussen,Anne Tybjærg‐Hansen,Børge G. Nordestgaard,Ruth Frikke‐Schmidt
标识
DOI:10.1016/j.jalz.2017.05.006
摘要
Abstract Introduction In recent prospective studies, low plasma levels of apolipoprotein E (apoE) are associated with high risk of dementia. Whether this reflects a causal association remains to be established. Methods Using a Mendelian randomization approach, we studied 106,562 and 75,260 individuals from the general population in observational and genetic analyses, respectively. Results In observational analyses risk of Alzheimer's disease and all dementia increased stepwise as a function of stepwise lower apoE levels ( P for trend, 2 × 10 −17 and 9 × 10 −21 ). APOE ‐weighted allele scores were associated with stepwise decreases in apoE ( P for trend, <1 × 10 −300 ). In instrumental variable analysis, the causal risk ratios for a 1 mg/dL genetically determined lower apoE were 1.41 (1.27–1.57) for Alzheimer's disease and 1.33 (1.25–1.43) for all dementia ( F ‐statistics = 3821). Discussion Genetic and hence lifelong low apoE is associated with high risk of dementia in the general population. The concordance between observational and genetic estimates suggests a potential causal relationship.
科研通智能强力驱动
Strongly Powered by AbleSci AI