Madrid Laura, Labrador Sandra C, González-Pérez Antonio, Sáez María E
CAEBi Bioinformática, Rio de la Plata 2, 41013 Sevilla, Spain.
Diagnostics (Basel). 2021 Dec 8;11(12):2303. doi: 10.3390/diagnostics11122303.
There is an urgent need to identify biomarkers for Alzheimer's disease (AD), but the identification of reliable blood-based biomarkers has proven to be much more difficult than initially expected. The current availability of high-throughput multi-omics data opens new possibilities in this titanic task. Candidate Single Nucleotide Polymorphisms (SNPs) from large, genome-wide association studies (GWAS), meta-analyses exploring AD (case-control design), and quantitative measures for cortical structure and general cognitive performance were selected. The Genotype-Tissue Expression (GTEx) database was used for identifying expression quantitative trait loci (eQTls) among candidate SNPs. Genes significantly regulated by candidate SNPs were investigated for differential expression in AD cases versus controls in the brain and plasma, both at the mRNA and protein level. This approach allowed us to identify candidate susceptibility factors and biomarkers of AD, facing experimental validation with more evidence than with genetics alone.
迫切需要确定阿尔茨海默病（AD）的生物标志物，但事实证明，确定可靠的血液生物标志物比最初预期的要困难得多。当前高通量多组学数据的可用性为这项艰巨任务带来了新的可能性。我们从大型全基因组关联研究（GWAS）、探索AD的荟萃分析（病例对照设计）以及皮质结构和一般认知表现的定量测量中选择了候选单核苷酸多态性（SNP）。基因型-组织表达（GTEx）数据库用于识别候选SNP中的表达定量性状位点（eQTL）。研究了受候选SNP显著调控的基因在AD病例与对照的大脑和血浆中mRNA和蛋白质水平的差异表达。这种方法使我们能够识别AD的候选易感性因素和生物标志物，相比于仅依靠遗传学，有更多证据面临实验验证。
