Department of Animal Science and Veterinary Medicine, College of Life Science, Longyan University, Longyan, Fujian, 364012, P.R. China.
Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI 96813, USA.
Hum Mol Genet. 2021 Dec 27;31(2):289-299. doi: 10.1093/hmg/ddab229.
Alzheimer's disease (ad) adversely affects the health, quality of life and independence of patients. There is a critical need to identify novel blood gene biomarkers for ad risk assessment. We performed a transcriptome-wide association study to identify biomarker candidates for ad risk. We leveraged two sets of gene expression prediction models of blood developed using different reference panels and modeling strategies. By applying the prediction models to a meta-GWAS including 71 880 (proxy) cases and 383 378 (proxy) controls, we identified significant associations of genetically determined expression of 108 genes in blood with ad risk. Of these, 15 genes were differentially expressed between ad patients and controls with concordant directions in measured expression data. With evidence from the analyses based on both genetic instruments and directly measured expression levels, this study identifies 15 genes with strong support as biomarkers in blood for ad risk, which may enhance ad risk assessment and mechanism-focused studies.
阿尔茨海默病（AD）严重影响患者的健康、生活质量和独立性。因此，迫切需要鉴定新型血液基因生物标志物，用于 AD 风险评估。我们进行了一项全转录组关联研究，以鉴定 AD 风险的生物标志物候选物。我们利用两套不同参考面板和建模策略开发的血液基因表达预测模型。通过将预测模型应用于包含 71880 例（代理）病例和 383378 例（代理）对照的荟萃 GWAS，我们确定了血液中 108 个基因的遗传决定表达与 AD 风险之间的显著关联。其中，15 个基因在 AD 患者和对照者之间的表达水平存在差异，且在测量表达数据中具有一致的方向。基于遗传工具和直接测量的表达水平的分析证据表明，本研究确定了 15 个具有强烈支持的基因作为血液中 AD 风险的生物标志物，这可能增强 AD 风险评估和以机制为重点的研究。
