Assessing the genetic contribution of cumulative behavioral factors associated with longitudinal type 2 diabetes risk highlights adiposity and the brain-metabolic axis.

medRxiv : the preprint server for health sciences
Authors
Keywords
Abstract

While genetic factors, behavior, and environmental exposures form a complex web of interrelated associations in type 2 diabetes (T2D), their interaction is poorly understood. Here, using data from ~500K participants of the UK Biobank, we identify the genetic determinants of a "polyexposure risk score" (PXS) a new risk factor that consists of an accumulation of 25 associated individual-level behaviors and environmental risk factors that predict longitudinal T2D incidence. PXS-T2D had a non-zero heritability (h = 0.18) extensive shared genetic architecture with established clinical and biological determinants of T2D, most prominently with body mass index (genetic correlation [r] = 0.57) and Homeostatic Model Assessment for Insulin Resistance (r = 0.51). Genetic loci associated with PXS-T2D were enriched for expression in the brain. Biobank scale data with genetic information illuminates how complex and cumulative exposures and behaviors as a whole impact T2D risk but whose biology have been elusive in genome-wide studies of T2D.

Year of Publication
2024
Journal
medRxiv : the preprint server for health sciences
Date Published
01/2024
DOI
10.1101/2024.01.30.24302019
PubMed ID
38352440
Links