TY - JOUR
T1 - The link between family history and risk of type 2 diabetes is not explained by anthropometric, lifestyle or genetic risk factors
T2 - The EPIC-InterAct study
AU - Scott, R. A.
AU - Langenberg, C.
AU - Sharp, S. J.
AU - Franks, P. W.
AU - Rolandsson, O.
AU - Drogan, D.
AU - van der Schouw, Y. T.
AU - Ekelund, U.
AU - Kerrison, N. D.
AU - Ardanaz, E.
AU - Arriola, L.
AU - Balkau, B.
AU - Barricarte, A.
AU - Barroso, I.
AU - Bendinelli, B.
AU - Beulens, J. W.J.
AU - Boeing, H.
AU - de Lauzon-Guillain, B.
AU - Deloukas, P.
AU - Fagherazzi, G.
AU - Gonzalez, C.
AU - Griffin, S. J.
AU - Groop, L. C.
AU - Halkjaer, J.
AU - Huerta, J. M.
AU - Kaaks, R.
AU - Khaw, K. T.
AU - Krogh, V.
AU - Nilsson, P. M.
AU - Norat, T.
AU - Overvad, K.
AU - Panico, S.
AU - Rodriguez-Suarez, L.
AU - Romaguera, D.
AU - Romieu, I.
AU - Sacerdote, C.
AU - Sánchez, M. J.
AU - Spijkerman, A. M.W.
AU - Teucher, B.
AU - Tjonneland, A.
AU - Tumino, R.
AU - van der A, D. L.
AU - Wark, P. A.
AU - McCarthy, M. I.
AU - Riboli, E.
AU - Wareham, N. J.
PY - 2013/1/1
Y1 - 2013/1/1
N2 - 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.
AB - 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.
KW - Family history
KW - Genetics
KW - Type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=84871612654&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s00125-012-2715-x
DO - https://doi.org/10.1007/s00125-012-2715-x
M3 - Article
C2 - 23052052
SN - 0012-186X
VL - 56
SP - 60
EP - 69
JO - Diabetologia
JF - Diabetologia
IS - 1
ER -