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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; He, Yixuan; Smadbeck, Patrick; Flannick, Jason; Mercader, Josep M; Udler, Miriam; Manrai, Arjun K; Moreno, Jordi; Patel, Chirag J.
Afiliación
  • Carvalho NRG; School of Biological Sciences; Georgia Institute of Technology; Atlanta, GA, 30332, USA.
  • He Y; Programs in Metabolism and Medical and Population Genetics, Broad Institute of Harvard and MIT, Boston, MA, 02142, USA.
  • Smadbeck P; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
  • Flannick J; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, 02114, USA.
  • Mercader JM; Programs in Metabolism and Medical and Population Genetics, Broad Institute of Harvard and MIT, Boston, MA, 02142, USA.
  • Udler M; Programs in Metabolism and Medical and Population Genetics, Broad Institute of Harvard and MIT, Boston, MA, 02142, USA.
  • Manrai AK; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, 02115, USA.
  • Moreno J; Department of Pediatrics, Harvard Medical School, Boston, MA, 02115, USA.
  • Patel CJ; Programs in Metabolism and Medical and Population Genetics, Broad Institute of Harvard and MIT, Boston, MA, 02142, USA.
medRxiv ; 2024 Jan 31.
Article en En | MEDLINE | ID: mdl-38352440
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 [rg] = 0.57) and Homeostatic Model Assessment for Insulin Resistance (rg = 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Idioma: En Revista: MedRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Idioma: En Revista: MedRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos