Genetic and Real-World Clinical Data, Combined with Empirical Validation, Nominate Jak-Stat Signaling as a Target for Alzheimer's Disease Therapeutic Development.

ABSTRACT: As genome-wide association studies (GWAS) have grown in size, the number of genetic variants that have been associated per disease has correspondingly increased. Despite this increase in the number of single-nucleotide polymorphisms (SNPs) identified per disease, their biological interpretation has in many cases remained elusive. To address this, we have combined GWAS results with orthogonal sources of evidence, namely the current knowledge of molecular pathways; real-world clinical data from six million patients; RNA expression across tissues from Alzheimer's disease (AD) patients, and purpose-built rodent models for experimental validation. In more detail, first we show that when examined at a pathway level, analysis of all GWAS studies groups AD in a cluster with disorders of immunity a

SUBMITTER: Nevado-Holgado AJ 

PROVIDER: S-EPMC6562942 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature