@article{9cda823390f54143bf86e6d0da398751,
title = "The link between family history and risk of type 2 diabetes is not explained by anthropometric, lifestyle or genetic risk factors: The EPIC-InterAct study",
abstract = "Aims/hypothesis: Although a family history of type 2 diabetes is a strong risk factor for the disease, the factors mediating this excess risk are poorly understood. In the InterAct case-cohort study, we investigated the association between a family history of diabetes among different family members and the incidence of type 2 diabetes, as well as the extent to which genetic, anthropometric and lifestyle risk factors mediated this association. Methods: A total of 13,869 individuals (including 6,168 incident cases of type 2 diabetes) had family history data available, and 6,887 individuals had complete data on all mediators. Country-specific Prentice-weighted Cox models were fitted within country, and HRs were combined using random effects meta-analysis. Lifestyle and anthropometric measurements were performed at baseline, and a genetic risk score comprising 35 polymorphisms associated with type 2 diabetes was created. Results: A family history of type 2 diabetes was associated with a higher incidence of the condition (HR 2.72, 95\% CI 2.48, 2.99). Adjustment for established risk factors including BMI and waist circumference only modestly attenuated this association (HR 2.44, 95\% CI 2.03, 2.95); the genetic score alone explained only 2\% of the family history-associated risk of type 2 diabetes. The greatest risk of type 2 diabetes was observed in those with a biparental history of type 2 diabetes (HR 5.14, 95\% CI 3.74, 7.07) and those whose parents had been diagnosed with diabetes at a younger age (<50 years; HR 4.69, 95\% CI 3.35, 6.58), an effect largely confined to a maternal family history. Conclusions/interpretation: Prominent lifestyle, anthropometric and genetic risk factors explained only a marginal proportion of the excess risk associated with family history, highlighting the fact that family history remains a strong, independent and easily assessed risk factor for type 2 diabetes. Discovering factors that will explain the association of family history with type 2 diabetes risk will provide important insight into the aetiology of type 2 diabetes.",
keywords = "Family history, Genetics, Type 2 diabetes",
author = "Scott, \{R. A.\} and C. Langenberg and Sharp, \{S. J.\} and Franks, \{P. W.\} and O. Rolandsson and D. Drogan and \{van der Schouw\}, \{Y. T.\} and U. Ekelund and Kerrison, \{N. D.\} and E. Ardanaz and L. Arriola and B. Balkau and A. Barricarte and I. Barroso and B. Bendinelli and Beulens, \{J. W.J.\} and H. Boeing and \{de Lauzon-Guillain\}, B. and P. Deloukas and G. Fagherazzi and C. Gonzalez and Griffin, \{S. J.\} and Groop, \{L. C.\} and J. Halkjaer and Huerta, \{J. M.\} and R. Kaaks and Khaw, \{K. T.\} and V. Krogh and Nilsson, \{P. M.\} and T. Norat and K. Overvad and S. Panico and L. Rodriguez-Suarez and D. Romaguera and I. Romieu and C. Sacerdote and S{\'a}nchez, \{M. J.\} and Spijkerman, \{A. M.W.\} and B. Teucher and A. Tjonneland and R. Tumino and \{van der A\}, \{D. L.\} and Wark, \{P. A.\} and McCarthy, \{M. I.\} and E. Riboli and Wareham, \{N. J.\}",
note = "Funding Information: Acknowledgements The authors would like to make the following acknowledgements. P.W. Franks: Swedish Research Council, Novo Nordisk, Swedish Diabetes Association and Swedish Heart-Lung Foundation; Y.T. van der Schouw: verification of diabetes cases was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht; L. Arriola: the participants of the Spanish EPIC cohort for their contribution to the study as well as to the team of trained nurses who participated in the recruitment; I. Barroso: Wellcome Trust grant 098051 and UK NIHR Cambridge Biomedical Research Centre; J.W.J. Beulens: verification of diabetes cases was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht; P. Deloukas: work was supported by the Wellcome Trust; L. Groop: Swedish Research Council; J. Halkjaer: Danish Cancer Society; J.M. Huerta: Health Research Fund of the Spanish Ministry of Health; Murcia Regional Government (no. 6236); CIBER Epidemiolog{\'i}a y Salud P{\'u}blica (CIBERESP), Spain; R. Kaaks: German Cancer Aid; K.T. Khaw: Medical Research Council UK, Cancer Research UK; P. Nilsson: Swedish Research Council; K. Overvad: Danish Cancer Society; L.Rodriguez-Suarez: Asturias Regional Government; A.M.W. Spijkerman: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands; B. Teucher: German Cancer Aid; A. Tjonneland: Danish Cancer Society; R. Tumino: AIRE-ONLUS Ragusa, AVIS-Ragusa, Sicilian Regional Government; D.L. van der A: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands; M.I. McCarthy: InterAct, Wellcome Trust (083270/Z/07/Z), MRC (G0601261) Funding The InterAct study received funding from the European Union (Integrated Project LSHM-CT-2006-037197 in the Framework Programme 6 of the European Community). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.",
year = "2013",
month = jan,
doi = "10.1007/s00125-012-2715-x",
language = "English",
volume = "56",
pages = "60--69",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Science and Business Media Deutschland GmbH",
number = "1",
}