RT Journal Article
T1 Gene-lifestyle interaction and type 2 diabetes: the EPIC interact case-cohort study.
A1 Langenberg, Claudia
A1 Sharp, Stephen J
A1 Franks, Paul W
A1 Scott, Robert A
A1 Deloukas, Panos
A1 Forouhi, Nita G
A1 Froguel, Philippe
A1 Groop, Leif C
A1 Hansen, Torben
A1 Palla, Luigi
A1 Pedersen, Oluf
A1 Schulze, Matthias B
A1 Tormo, Maria-Jose
A1 Wheeler, Eleanor
A1 Agnoli, Claudia
A1 Arriola, Larraitz
A1 Barricarte, Aurelio
A1 Boeing, Heiner
A1 Clarke, Geraldine M
A1 Clavel-Chapelon, Françoise
A1 Duell, Eric J
A1 Fagherazzi, Guy
A1 Kaaks, Rudolf
A1 Kerrison, Nicola D
A1 Key, Timothy J
A1 Khaw, Kay Tee
A1 Kröger, Janine
A1 Lajous, Martin
A1 Morris, Andrew P
A1 Navarro, Carmen
A1 Nilsson, Peter M
A1 Overvad, Kim
A1 Palli, Domenico
A1 Panico, Salvatore
A1 Quirós, J Ramón
A1 Rolandsson, Olov
A1 Sacerdote, Carlotta
A1 Sanchez-Perez, Maria-Jose
A1 Slimani, Nadia
A1 Spijkerman, Annemieke M W
A1 Tumino, Rosario
A1 van der A, Daphne L
A1 van der Schouw, Yvonne T
A1 Barroso, Inês
A1 McCarthy, Mark I
A1 Riboli, Elio
A1 Wareham, Nicholas J
K1 Alelos
K1 Índice de Masa Corporal
K1 Estudios de Cohortes
K1 Diabetes Mellitus Tipo 2
K1 Dieta Mediterránea
K1 Femenino
K1 Predisposición Genética a la Enfermedad
K1 Humanos
K1 Estilo de Vida
K1 Masculino
K1 Mediana Edad
K1 Actividad Motora
K1 Polimorfismo de Nucleótido Simple
K1 Modelos de Riesgos Proporcionales
K1 Factores de Riesgo
K1 Circunferencia de la Cintura
AB BACKGROUNDUnderstanding of the genetic basis of type 2 diabetes (T2D) has progressed rapidly, but the interactions between common genetic variants and lifestyle risk factors have not been systematically investigated in studies with adequate statistical power. Therefore, we aimed to quantify the combined effects of genetic and lifestyle factors on risk of T2D in order to inform strategies for prevention.METHODS AND FINDINGSThe InterAct study includes 12,403 incident T2D cases and a representative sub-cohort of 16,154 individuals from a cohort of 340,234 European participants with 3.99 million person-years of follow-up. We studied the combined effects of an additive genetic T2D risk score and modifiable and non-modifiable risk factors using Prentice-weighted Cox regression and random effects meta-analysis methods. The effect of the genetic score was significantly greater in younger individuals (p for interaction  = 1.20×10-4). Relative genetic risk (per standard deviation [4.4 risk alleles]) was also larger in participants who were leaner, both in terms of body mass index (p for interaction  = 1.50×10-3) and waist circumference (p for interaction  = 7.49×10-9). Examination of absolute risks by strata showed the importance of obesity for T2D risk. The 10-y cumulative incidence of T2D rose from 0.25% to 0.89% across extreme quartiles of the genetic score in normal weight individuals, compared to 4.22% to 7.99% in obese individuals. We detected no significant interactions between the genetic score and sex, diabetes family history, physical activity, or dietary habits assessed by a Mediterranean diet score.CONCLUSIONSThe relative effect of a T2D genetic risk score is greater in younger and leaner participants. However, this sub-group is at low absolute risk and would not be a logical target for preventive interventions. The high absolute risk associated with obesity at any level of genetic risk highlights the importance of universal rather than targeted approaches to lifestyle intervention.
PB Public Library of Science
SN 1549-1277
YR 2014
FD 2014-05-20
LK http://hdl.handle.net/10668/1797
UL http://hdl.handle.net/10668/1797
LA en
NO Langenberg C, Sharp SJ, Franks PW, Scott RA, Deloukas P, Forouhi NG, et al. Gene-lifestyle interaction and type 2 diabetes: the EPIC interact case-cohort study. PLoS Med.. 2014 ; 11(5):e1001647
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 19, 2025