Douglas Mental Health University Institute, Montréal, Québec, Canada; Centre for the Studies in the Prevention of Alzheimer's Disease, Montréal, Québec, Canada; McGill University, Montréal, Québec, Canada.
Douglas Mental Health University Institute, Montréal, Québec, Canada; McGill University, Montréal, Québec, Canada.
Alzheimers Dement. 2018 Jun;14(6):787-796. doi: 10.1016/j.jalz.2017.12.004. Epub 2018 Jan 19.
Because currently known Alzheimer's disease (AD) single-nucleotide polymorphisms only account for a small fraction of the genetic variance in this disease, there is a need to identify new variants associated with AD.
Our team performed a genome-wide association study in the Quebec Founder Population isolate to identify novel protective or risk genetic factors for late-onset sporadic AD and examined the impact of these variants on gene expression and AD pathology.
The rs10984186 variant is associated with an increased risk of developing AD and with a higher CDK5RAP2 mRNA prevalence in the hippocampus. On the other hand, the rs4837766 variant, which is among the best cis-expression quantitative trait loci in the CDK5RAP2 gene, is associated with lower mild cognitive impairment/AD risk and conversion rate.
The rs10984186 risk and rs4837766 protective polymorphic variants of the CDK5RAP2 gene might act as potent genetic modifiers for AD risk and/or conversion by modulating the expression of this gene.
由于目前已知的阿尔茨海默病（AD）单核苷酸多态性仅占该疾病遗传变异的一小部分，因此需要确定与 AD 相关的新变体。
我们的团队在魁北克创始人群体隔离区进行了全基因组关联研究，以确定晚发性散发性 AD 的新的保护性或风险遗传因素，并研究这些变体对基因表达和 AD 病理的影响。
rs10984186 变体与 AD 发病风险增加以及海马体中 CDK5RAP2 mRNA 患病率升高相关。另一方面，rs4837766 变体是 CDK5RAP2 基因中最好的顺式表达数量性状基因座之一，与较低的轻度认知障碍/AD 风险和转化率相关。
CDK5RAP2 基因的 rs10984186 风险和 rs4837766 保护性多态变体可能通过调节该基因的表达，作为 AD 风险和/或转化的有效遗传修饰因子。
