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A transcriptome-wide association study identifies novel blood-based gene biomarker candidates for Alzheimer’s disease risk
Human Molecular Genetics ( IF 3.1 ) Pub Date : 2021-08-09 , DOI: 10.1093/hmg/ddab229
Yanfa Sun 1, 2, 3, 4 , Dan Zhou 5 , Md Rezanur Rahman 6 , Jingjing Zhu 2 , Dalia Ghoneim 2 , Nancy J Cox 5 , Thomas G Beach 7 , Chong Wu 8 , Eric R Gamazon 5, 9, 10 , Lang Wu 2
Affiliation  

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.

中文翻译:

一项全转录组关联研究确定了阿尔茨海默病风险的新型血液基因生物标志物候选者

阿尔茨海默病 (ad) 对患者的健康、生活质量和独立性产生不利影响。迫切需要确定用于广告风险评估的新型血液基因生物标志物。我们进行了一项转录组范围的关联研究,以确定广告风险的候选生物标志物。我们利用了两组使用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括 71 880 例(代理)病例和 383 378 例(代理)对照的元 GWAS,我们确定了血液中 108 个基因的遗传决定表达与广告风险的显着关联。其中,15 个基因在广告患者和对照之间差异表达,在测量的表达数据中具有一致的方向。
更新日期:2021-08-09
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