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

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 (h² = 0.18) extensive shared genetic architecture with established clinical and biological determinants of T2D, most prominently with body mass index (genetic correlation [r_g] = 0.57) and Homeostatic Model Assessment for Insulin Resistance (r_g = 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.

SUBMITTER: Carvalho NRG

PROVIDER: S-EPMC10863013 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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

Carvalho Nuno R G NRG He Yixuan Y Smadbeck Patrick P Flannick Jason J Mercader Josep M JM Udler Miriam M Manrai Arjun K AK Moreno Jordi J Patel Chirag J CJ

medRxiv : the preprint server for health sciences 20240131

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 h ...[more]

PMID: 38352440

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Dataset Information

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

Publications

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

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