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Title: Gene-Lifestyle Interaction and Type 2 Diabetes: The EPIC InterAct Case-Cohort Study
Author: Langenberg, Claudia
Sharp, Stephen J.
Franks, Paul W.
Scott, Robert A.
Deloukas, Panos
Forouhi, Nita G.
Froguel, Philippe
Groop, Leif C.
Hansen, Torben
Palla, Luigi
Pedersen, Oluf
Schulze, Matthias B.
Tormo, Maria José
Wheeler, Eleanor
Agnoli, Claudia
Arriola, Larraitz
Barricarte, Aurelio
Boeing, Heiner
Clarke, Geraldine M.
Clavel-Chapelon, Françoise
Duell, Eric J.
Fagherazzi, Guy
Kaaks, Rudolf
Kerrison, Nicola D.
Key, Timothy J.
Khaw, Kay-Tee
Kröger, Janine
Lajous, Martin
Morris, Andrew P.
Navarro, Carmen
Nilsson, Peter M.
Overvad, Kim
Palli, Domenico
Panico, Salvatore
Quirós, J. Ramón
Rolandsson, Olov
Sacerdote, Carlotta
Sánchez, María José
Slimani, Nadia
Spijkerman, Annemieke M. W.
Tumino, Rosario
van der A, Daphne L.
van der Schouw, Yvonne T.
Barroso, Inês
McCarthy, Mark I.
Riboli, Elio
Wareham, Nicholas J.
Keywords: Diabetis no-insulinodependent
Non-insulin-dependent diabetes
Issue Date: May-2014
Publisher: Public Library of Science (PLoS)
Abstract: Background: Understanding 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 Findings: The 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 = 1.20x10(-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 = 1.50x10(-3)) and waist circumference (p for interaction = 7.49x10(-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. Conclusions: The relative effect of a T2D genetic risk score is greater in younger and leaner participants. However, this subgroup 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.
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It is part of: PLoS Medicine, 2014, vol. 11, num. 5, p. e1001647
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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