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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.

A transcriptome-wide association study identifies novel blood-based gene biomarker candidates for Alzheimer’s disease risk