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. Fagherazzi & 26 others C. 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 journalArticle

    81 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)60-69
    Number of pages10
    JournalDiabetologia
    Volume56
    Issue number1
    Early online date28 Sep 2012
    DOIs
    Publication statusPublished - Jan 2013

    Fingerprint

    Type 2 Diabetes Mellitus
    Life Style
    Incidence
    Waist Circumference
    Proportional Hazards Models
    Meta-Analysis
    Cohort Studies
    Parents
    Mothers

    Keywords

    • Family history
    • Genetics
    • Type 2 diabetes

    ASJC Scopus subject areas

    • Internal Medicine
    • Endocrinology, Diabetes and Metabolism

    Cite this

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

    In: Diabetologia, Vol. 56, No. 1, 01.2013, p. 60-69.

    Research output: Contribution to journalArticle

    Scott, RA, Langenberg, C, Sharp, SJ, Franks, PW, Rolandsson, O, Drogan, D, van der Schouw, YT, Ekelund, U, Kerrison, ND, Ardanaz, E, Arriola, L, Balkau, B, Barricarte, A, Barroso, I, Bendinelli, B, Beulens, JWJ, Boeing, H, de Lauzon-Guillain, B, Deloukas, P, Fagherazzi, G, Gonzalez, C, Griffin, SJ, Groop, LC, Halkjaer, J, Huerta, JM, Kaaks, R, Khaw, KT, Krogh, V, Nilsson, PM, Norat, T, Overvad, K, Panico, S, Rodriguez-Suarez, L, Romaguera, D, Romieu, I, Sacerdote, C, Sánchez, MJ, Spijkerman, AMW, Teucher, B, Tjonneland, A, Tumino, R, van der A, DL, Wark, PA, McCarthy, MI, Riboli, E & Wareham, NJ 2013, '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' Diabetologia, vol. 56, no. 1, pp. 60-69. https://doi.org/10.1007/s00125-012-2715-x
    Scott, R. A. ; Langenberg, C. ; Sharp, S. J. ; Franks, P. W. ; Rolandsson, O. ; Drogan, D. ; van der Schouw, Y. T. ; Ekelund, U. ; Kerrison, N. D. ; Ardanaz, E. ; Arriola, L. ; Balkau, B. ; Barricarte, A. ; Barroso, I. ; Bendinelli, B. ; Beulens, J. W J ; Boeing, H. ; de Lauzon-Guillain, B. ; Deloukas, P. ; Fagherazzi, G. ; Gonzalez, C. ; Griffin, S. J. ; Groop, L. C. ; Halkjaer, J. ; Huerta, J. M. ; Kaaks, R. ; Khaw, K. T. ; Krogh, V. ; Nilsson, P. M. ; Norat, T. ; Overvad, K. ; Panico, S. ; Rodriguez-Suarez, L. ; Romaguera, D. ; Romieu, I. ; Sacerdote, C. ; Sánchez, M. J. ; Spijkerman, A. M W ; Teucher, B. ; Tjonneland, A. ; Tumino, R. ; van der A, D. L. ; Wark, P. A. ; McCarthy, M. I. ; Riboli, E. ; Wareham, N. J. / 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. In: Diabetologia. 2013 ; Vol. 56, No. 1. pp. 60-69.
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    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.",
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    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.}",
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    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

    Y1 - 2013/1

    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

    U2 - 10.1007/s00125-012-2715-x

    DO - 10.1007/s00125-012-2715-x

    M3 - Article

    VL - 56

    SP - 60

    EP - 69

    JO - Diabetologia

    JF - Diabetologia

    SN - 0012-186X

    IS - 1

    ER -