Gene-lifestyle interaction and type 2 diabetes: the EPIC interact case-cohort study.
<h4>Background</h4>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...
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Public Library of Science (PLoS)
2014
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oai:doaj.org-article:71aca260f1344d77944bf5b7a26561e32021-11-11T05:42:19ZGene-lifestyle interaction and type 2 diabetes: the EPIC interact case-cohort study.1549-12771549-167610.1371/journal.pmed.1001647https://doaj.org/article/71aca260f1344d77944bf5b7a26561e32014-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24845081/?tool=EBIhttps://doaj.org/toc/1549-1277https://doaj.org/toc/1549-1676<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.Claudia LangenbergStephen J SharpPaul W FranksRobert A ScottPanos DeloukasNita G ForouhiPhilippe FroguelLeif C GroopTorben HansenLuigi PallaOluf PedersenMatthias B SchulzeMaria-Jose TormoEleanor WheelerClaudia AgnoliLarraitz ArriolaAurelio BarricarteHeiner BoeingGeraldine M ClarkeFrançoise Clavel-ChapelonEric J DuellGuy FagherazziRudolf KaaksNicola D KerrisonTimothy J KeyKay Tee KhawJanine KrögerMartin LajousAndrew P MorrisCarmen NavarroPeter M NilssonKim OvervadDomenico PalliSalvatore PanicoJ Ramón QuirósOlov RolandssonCarlotta SacerdoteMaría-José SánchezNadia SlimaniAnnemieke M W SpijkermanRosario TuminoDaphne L van der AYvonne T van der SchouwInês BarrosoMark I McCarthyElio RiboliNicholas J WarehamPublic Library of Science (PLoS)articleMedicineRENPLoS Medicine, Vol 11, Iss 5, p e1001647 (2014) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R |
| spellingShingle |
Medicine R Claudia Langenberg Stephen J Sharp Paul W Franks Robert A Scott Panos Deloukas Nita G Forouhi Philippe Froguel Leif C Groop Torben Hansen Luigi Palla Oluf Pedersen Matthias B Schulze Maria-Jose Tormo Eleanor Wheeler Claudia Agnoli Larraitz Arriola Aurelio Barricarte Heiner Boeing Geraldine M Clarke Françoise Clavel-Chapelon Eric J Duell Guy Fagherazzi Rudolf Kaaks Nicola D Kerrison Timothy J Key Kay Tee Khaw Janine Kröger Martin Lajous Andrew P Morris Carmen Navarro Peter M Nilsson Kim Overvad Domenico Palli Salvatore Panico J Ramón Quirós Olov Rolandsson Carlotta Sacerdote María-José Sánchez Nadia Slimani Annemieke M W Spijkerman Rosario Tumino Daphne L van der A Yvonne T van der Schouw Inês Barroso Mark I McCarthy Elio Riboli Nicholas J Wareham Gene-lifestyle interaction and type 2 diabetes: the EPIC interact case-cohort study. |
| description |
<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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. |
| format |
article |
| author |
Claudia Langenberg Stephen J Sharp Paul W Franks Robert A Scott Panos Deloukas Nita G Forouhi Philippe Froguel Leif C Groop Torben Hansen Luigi Palla Oluf Pedersen Matthias B Schulze Maria-Jose Tormo Eleanor Wheeler Claudia Agnoli Larraitz Arriola Aurelio Barricarte Heiner Boeing Geraldine M Clarke Françoise Clavel-Chapelon Eric J Duell Guy Fagherazzi Rudolf Kaaks Nicola D Kerrison Timothy J Key Kay Tee Khaw Janine Kröger Martin Lajous Andrew P Morris Carmen Navarro Peter M Nilsson Kim Overvad Domenico Palli Salvatore Panico J Ramón Quirós Olov Rolandsson Carlotta Sacerdote María-José Sánchez Nadia Slimani Annemieke M W Spijkerman Rosario Tumino Daphne L van der A Yvonne T van der Schouw Inês Barroso Mark I McCarthy Elio Riboli Nicholas J Wareham |
| author_facet |
Claudia Langenberg Stephen J Sharp Paul W Franks Robert A Scott Panos Deloukas Nita G Forouhi Philippe Froguel Leif C Groop Torben Hansen Luigi Palla Oluf Pedersen Matthias B Schulze Maria-Jose Tormo Eleanor Wheeler Claudia Agnoli Larraitz Arriola Aurelio Barricarte Heiner Boeing Geraldine M Clarke Françoise Clavel-Chapelon Eric J Duell Guy Fagherazzi Rudolf Kaaks Nicola D Kerrison Timothy J Key Kay Tee Khaw Janine Kröger Martin Lajous Andrew P Morris Carmen Navarro Peter M Nilsson Kim Overvad Domenico Palli Salvatore Panico J Ramón Quirós Olov Rolandsson Carlotta Sacerdote María-José Sánchez Nadia Slimani Annemieke M W Spijkerman Rosario Tumino Daphne L van der A Yvonne T van der Schouw Inês Barroso Mark I McCarthy Elio Riboli Nicholas J Wareham |
| author_sort |
Claudia Langenberg |
| title |
Gene-lifestyle interaction and type 2 diabetes: the EPIC interact case-cohort study. |
| title_short |
Gene-lifestyle interaction and type 2 diabetes: the EPIC interact case-cohort study. |
| title_full |
Gene-lifestyle interaction and type 2 diabetes: the EPIC interact case-cohort study. |
| title_fullStr |
Gene-lifestyle interaction and type 2 diabetes: the EPIC interact case-cohort study. |
| title_full_unstemmed |
Gene-lifestyle interaction and type 2 diabetes: the EPIC interact case-cohort study. |
| title_sort |
gene-lifestyle interaction and type 2 diabetes: the epic interact case-cohort study. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/71aca260f1344d77944bf5b7a26561e3 |
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