Gene-lifestyle interaction and type 2 diabetes: the EPIC interact case-cohort study
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Gene-lifestyle interaction and type 2 diabetes : the EPIC interact case-cohort study. / 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-Jose; 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.
In: P L o S Medicine (Print), Vol. 11, No. 5, e1001647, 2014.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Gene-lifestyle interaction and type 2 diabetes
T2 - the EPIC interact case-cohort study
AU - Langenberg, Claudia
AU - Sharp, Stephen J
AU - Franks, Paul W
AU - Scott, Robert A
AU - Deloukas, Panos
AU - Forouhi, Nita G
AU - Froguel, Philippe
AU - Groop, Leif C
AU - Hansen, Torben
AU - Palla, Luigi
AU - Pedersen, Oluf
AU - Schulze, Matthias B
AU - Tormo, Maria-Jose
AU - Wheeler, Eleanor
AU - Agnoli, Claudia
AU - Arriola, Larraitz
AU - Barricarte, Aurelio
AU - Boeing, Heiner
AU - Clarke, Geraldine M
AU - Clavel-Chapelon, Françoise
AU - Duell, Eric J
AU - Fagherazzi, Guy
AU - Kaaks, Rudolf
AU - Kerrison, Nicola D
AU - Key, Timothy J
AU - Khaw, Kay Tee
AU - Kröger, Janine
AU - Lajous, Martin
AU - Morris, Andrew P
AU - Navarro, Carmen
AU - Nilsson, Peter M
AU - Overvad, Kim
AU - Palli, Domenico
AU - Panico, Salvatore
AU - Quirós, J Ramón
AU - Rolandsson, Olov
AU - Sacerdote, Carlotta
AU - Sánchez, María-José
AU - Slimani, Nadia
AU - Spijkerman, Annemieke M W
AU - Tumino, Rosario
AU - van der A, Daphne L
AU - van der Schouw, Yvonne T
AU - Barroso, Inês
AU - McCarthy, Mark I
AU - Riboli, Elio
AU - Wareham, Nicholas J
PY - 2014
Y1 - 2014
N2 - 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 = 1.20×10-4). 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.CONCLUSIONS: The 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.
AB - 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 = 1.20×10-4). 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.CONCLUSIONS: The 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.
KW - Alleles
KW - Body Mass Index
KW - Cohort Studies
KW - Diabetes Mellitus, Type 2
KW - Diet, Mediterranean
KW - Female
KW - Genetic Predisposition to Disease
KW - Humans
KW - Life Style
KW - Male
KW - Middle Aged
KW - Motor Activity
KW - Polymorphism, Single Nucleotide
KW - Proportional Hazards Models
KW - Risk Factors
KW - Waist Circumference
U2 - 10.1371/journal.pmed.1001647
DO - 10.1371/journal.pmed.1001647
M3 - Journal article
C2 - 24845081
VL - 11
JO - P L o S Medicine (Online)
JF - P L o S Medicine (Online)
SN - 1549-1277
IS - 5
M1 - e1001647
ER -
ID: 137907567