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Genetic predisposition to adiposity, and type 2 diabetes: the role of lifestyle and phenotypic adiposity

dc.contributor.authorZhang, Mengrong
dc.contributor.authorWard, Joey
dc.contributor.authorStrawbridge, Rona J.
dc.contributor.authorAnderson, Jana J.
dc.contributor.authorCelis-Morales, Carlos
dc.contributor.authorPell, Jill P.
dc.contributor.authorHo, Frederick K.
dc.contributor.authorLyall, Donald M
dc.date.accessioned2025-07-07T18:23:12Z
dc.date.available2025-07-07T18:23:12Z
dc.date.issued2025
dc.identifier.urihttp://repositorio.ucm.cl/handle/ucm/6204
dc.description.abstractAims Genetic predisposition to adiposity is associated with type 2 diabetes (T2D), even in the absence of phenotypic adiposity (obesity and central obesity). We aimed to quantify the overall contribution of obesity and modifiable lifestyle factors to the association between genetic predisposition to adiposity and the development of T2D. Methods This prospective cohort study involved 220 703 White British participants from the UK Biobank. It examined the associations between genetic predisposition to adiposity [body mass index polygenic risk (BMI-PRS) and waist–hip ratio polygenic risk (WHR-PRS)] and incident T2D, as well as interactions and mediation via lifestyle factors (diet quality, physical activity levels, total energy intake, sleep duration, and smoking and alcohol intake) and phenotypic adiposity. Results People with high phenotypic adiposity and high adiposity PRS values (>1 SD above the mean) had the highest risk of incident T2D (versus non-obese/central obese and non-high PRS). This was the case for BMI-PRS [hazard ratio (HR) = 3.72] and WHR-PRS (HR = 4.17). Lifestyle factors explained 30.5% of the BMI-PRS/T2D association (2.0% mediation; 28.5% effect modification), and lifestyle and obesity together explained 92.1% (78.8% mediation; 13.3% effect modification). Lifestyle factors explained 20.4% of the WHR-PRS/T2D association (3.4% mediation; 17.0% effect modification), and lifestyle and central obesity together explained 72.8% (41.1% mediation; 31.7% effect modification). Conclusions Whilst phenotypic adiposity explains a large proportion of the association between BMI-PRS/WHR-PRS and T2D, modifiable lifestyle factors also make contributions. Promoting healthy lifestyles among people prone to adiposity is important in reducing the global burden of T2D.es_CL
dc.language.isoenes_CL
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 Chile*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/*
dc.sourceEuropean Journal of Endocrinology, 192(5), 549-557es_CL
dc.subjectT2Des_CL
dc.subjectObesityes_CL
dc.subjectCentral obesityes_CL
dc.subjectBMI-PRSes_CL
dc.subjectWHR-PRSes_CL
dc.subjectLifestyle factorses_CL
dc.subjectAdiposityes_CL
dc.titleGenetic predisposition to adiposity, and type 2 diabetes: the role of lifestyle and phenotypic adiposityes_CL
dc.typeArticlees_CL
dc.ucm.indexacionScopuses_CL
dc.ucm.indexacionIsies_CL
dc.ucm.urioxfordjournals.ucm.elogim.com/ejendo/article/192/5/549/8124079es_CL
dc.ucm.doidoi.org/10.1093/ejendo/lvaf084es_CL


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Atribución-NoComercial-SinDerivadas 3.0 Chile
Excepto si se señala otra cosa, la licencia de la publicación se describe como Atribución-NoComercial-SinDerivadas 3.0 Chile