Gene-Lifestyle Interaction and Type 2 Diabetes the EPIC InterAct Case-Cohort Study

doi:10.1371/journal.pmed.1001647

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Fältnamn	Indikatorer	Metadata
000		05640naa a22010093a 4500
001		22071628
003		SE-LIBR
005		20171206202715.0
007		cr\|\|\|\|\|\|\|\|\|\|\|\|
008		171206s2014 sw \|\|\|\| o \|\|\|\| \|\|eng c
024	7	a http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-912262 uri
024	7	a urn:nbn:se:umu:diva-912262 urn
024	7	a 10.1371/journal.pmed.10016472 doi
040		a S
041	0	a eng
042		9 EPLK
100	1	a Langenberg, Claudia4 aut
245	1 0	a Gene-Lifestyle Interaction and Type 2 Diabetesh [Elektronisk resurs]b the EPIC InterAct Case-Cohort Study
260		c 2014
500		a Published
506	0	a gratis
520		a 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.
650	7	a Medical and Health Sciences2 hsv
650	7	a Clinical Medicine2 hsv
650	7	a Endocrinology and Diabetes2 hsv
650	7	a Medicin och hälsovetenskap2 hsv
650	7	a Klinisk medicin2 hsv
650	7	a Endokrinologi och diabetes2 hsv
700	1	a Sharp, Stephen J.4 aut
700	1	a Franks, Paul W.4 aut
700	1	a Scott, Robert A.4 aut
700	1	a Deloukas, Panos4 aut
700	1	a Forouhi, Nita G.4 aut
700	1	a Froguel, Philippe4 aut
700	1	a Groop, Leif C.4 aut
700	1	a Hansen, Torben4 aut
700	1	a Palla, Luigi4 aut
700	1	a Pedersen, Oluf4 aut
700	1	a Schulze, Matthias B.4 aut
700	1	a Tormo, Maria-Jose4 aut
700	1	a Wheeler, Eleanor4 aut
700	1	a Agnoli, Claudia4 aut
700	1	a Arriola, Larraitz4 aut
700	1	a Barricarte, Aurelio4 aut
700	1	a Boeing, Heiner4 aut
700	1	a Clarke, Geraldine M.4 aut
700	1	a Clavel-Chapelon, Francoise4 aut
700	1	a Duell, Eric J.4 aut
700	1	a Fagherazzi, Guy4 aut
700	1	a Kaaks, Rudolf4 aut
700	1	a Kerrison, Nicola D.4 aut
700	1	a Key, Timothy J.4 aut
700	1	a Khaw, Kay Tee4 aut
700	1	a Kroeger, Janine4 aut
700	1	a Lajous, Martin4 aut
700	1	a Morris, Andrew P.4 aut
700	1	a Navarro, Carmen4 aut
700	1	a Nilsson, Peter M.4 aut
700	1	a Overvad, Kim4 aut
700	1	a Palli, Domenico4 aut
700	1	a Panico, Salvatore4 aut
700	1	a Quiros, J. Ramon4 aut
700	1	a Rolandsson, Olov4 aut
700	1	a Sacerdote, Carlotta4 aut
700	1	a Sanchez, Maria-Jose4 aut
700	1	a Slimani, Nadia4 aut
700	1	a Spijkerman, Annemieke M. W.4 aut
700	1	a Tumino, Rosario4 aut
700	1	a van der A, Daphne L.4 aut
700	1	a van der Schouw, Yvonne T.4 aut
700	1	a Barroso, Ines4 aut
700	1	a McCarthy, Mark I.4 aut
700	1	a Riboli, Elio4 aut
700	1	a Wareham, Nicholas J.4 aut
710	1 2	a Umeå universitetb Medicinska fakulteten4 pbl0 268483
710	1 2	a Umeå universitetb Medicinska fakulteten4 pbl0 268483
772	1 8	i channel recordw 18813935
773	0 8	i Värdpublikationt PLoS Medicineg 11:5x 1549-1277
856	4 0	u http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-91226
856	4 0	u http://dx.doi.org/10.1371/journal.pmed.1001647
856	4 0	u http://umu.diva-portal.org/smash/get/diva2:734800/FULLTEXT01
910	2 s	6 710,710a Umeå universitet.b Medicinsk-odontologiska fakultetenu Umeå universitet.b Medicinska fakulteten
910	2 s	6 710,710a Medicinska fakulteten vid Umeå universitetu Umeå universitet.b Medicinska fakulteten
841		5 APISa x ab 171206\|\|0000\|\|\|\|\|001\|\|\|\|\|\|000000e 1
024	7	5 APISa urn:nbn:se:umu:diva-912262 urn
852		5 APISb APIS
856	4 0	5 APISu http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-91226

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Av författaren/redakt...: Langenberg, Clau ...; Sharp, Stephen J ...; Franks, Paul W.; Scott, Robert A.; Deloukas, Panos; Forouhi, Nita G.; visa fler...; Froguel, Philipp ...; Groop, Leif C.; Hansen, Torben; Palla, Luigi; Pedersen, Oluf; Schulze, Matthia ...; Tormo, Maria-Jos ...; Wheeler, Eleanor; Agnoli, Claudia; Arriola, Larrait ...; Barricarte, Aure ...; Boeing, Heiner; Clarke, Geraldin ...; Clavel-Chapelon, ...; Duell, Eric J.; Fagherazzi, Guy; Kaaks, Rudolf; Kerrison, Nicola ...; Key, Timothy J.; Khaw, Kay Tee; Kroeger, Janine; Lajous, Martin; Morris, Andrew P ...; Navarro, Carmen; Nilsson, Peter M ...; Overvad, Kim; Palli, Domenico; Panico, Salvator ...; Quiros, J. Ramon; Rolandsson, Olov; Sacerdote, Carlo ...; Sanchez, Maria-J ...; Slimani, Nadia; Spijkerman, Anne ...; Tumino, Rosario; van der A, Daphn ...; van der Schouw, ...; Barroso, Ines; McCarthy, Mark I ...; Riboli, Elio; Wareham, Nichola ...; visa färre...

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