Decoding polygenic diseases: advances in noncoding variant prioritization and validation.

Genome-wide association studies (GWASs) provide a key foundation for elucidating the genetic underpinnings of common polygenic diseases. However, these studies have limitations in their ability to assign causality to particular genetic variants, especially those residing in the noncoding genome. Over the past decade, technological and methodological advances in both analytical and empirical prioritization of noncoding variants have enabled the identification of causative variants by leveraging orthogonal functional evidence at increasing scale.

FOXO3 regulates a common genomic program in aging and glioblastoma stem cells.

Background: Glioblastoma (GBM) is an aggressive, age-associated malignant glioma that contains populations of cancer stem cells. These glioma stem cells (GSCs) evade therapeutic interventions and repopulate tumors due to their existence in a slowly cycling quiescent state. Although aging is well known to increase cancer initiation, the extent to which the mechanisms supporting GSC tumorigenicity are related to physiological aging remains unknown.

FOXO3 directly regulates an autophagy network to functionally regulate proteostasis in adult neural stem cells.

Maintenance of a healthy proteome is essential for cellular homeostasis and loss of proteostasis is associated with tissue dysfunction and neurodegenerative disease. The mechanisms that support proteostasis in healthy cells and how they become defective during aging or in disease states are not fully understood. Here, we investigate the transcriptional programs that are essential for neural stem and progenitor cell (NSPC) function and uncover a program of autophagy genes under the control of the transcription factor FOXO3.