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

R. A. Scott, C. Langenberg, S. J. Sharp, P. W. Franks, O. Rolandsson, D. Drogan, Y. T. van der Schouw, U. Ekelund, N. D. Kerrison, E. Ardanaz, L. Arriola, B. Balkau, A. Barricarte, I. Barroso, B. Bendinelli, J. W J Beulens, H. Boeing, B. de Lauzon-Guillain, P. Deloukas, G. FagherazziC. Gonzalez, S. J. Griffin, L. C. Groop, J. Halkjaer, J. M. Huerta, R. Kaaks, K. T. Khaw, V. Krogh, P. M. Nilsson, T. Norat, K. Overvad, S. Panico, L. Rodriguez-Suarez, D. Romaguera, I. Romieu, C. Sacerdote, M. J. Sánchez, A. M W Spijkerman, B. Teucher, A. Tjonneland, R. Tumino, D. L. van der A, P. A. Wark, M. I. McCarthy, E. Riboli, N. J. Wareham

Research output: Contribution to journalArticlepeer-review

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 (

Original languageEnglish
Pages (from-to)60-69
Number of pages10
JournalDiabetologia
Volume56
Issue number1
DOIs
Publication statusPublished - Jan 2013

Keywords

  • Family history
  • Genetics
  • Type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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