Epidemiology and genetic determinants of progressive deterioration of glycaemia in American Indians: The Strong Heart Family Study

N. Franceschini, K. Haack, H. H.H. Göring, V. S. Voruganti, S. Laston, L. Almasy, E. T. Lee, L. G. Best, R. R. Fabsitz, K. E. North, J. W. MacCluer, J. B. Meigs, J. S. Pankow, S. A. Cole

    Research output: Contribution to journalArticlepeer-review

    6 Scopus citations

    Abstract

    Aims/hypothesis: Type 2 diabetes is a chronic, heterogeneous disease and a major risk factor for cardiovascular diseases. The underlying mechanisms leading to progression to type 2 diabetes are not fully understood and genetic tools may help to identify important pathways of glycaemic deterioration. Methods: Using prospective data on American Indians from the Strong Heart Family Study, we identified 373 individuals defined as progressors (diabetes incident cases), 566 individuals with transitory impaired fasting glucose (IFG) and 1,011 controls (normal fasting glycaemia at all visits). We estimated the heritability (h2) of the traits and the evidence for association with 16 known variants identified in type 2 diabetes genome-wide association studies. Results: We noted high h2 for diabetes progression (h2 = 0.65 ± 0.16, p = 2.7 × 10-6) but little contribution of genetic factors to transitory IFG (h2 = 0.09 ± 0.10, p = 0.19) for models adjusted for multiple risk factors. At least three variants (in WFS1, TSPAN8 and THADA) were nominally associated with diabetes progression in age- and sex-adjusted analyses with estimates showing the same direction of effects as reported in the discovery European ancestry studies. Conclusions/interpretation: Our findings do not exclude these loci for diabetes susceptibility in American Indians and suggest phenotypic heterogeneity of the IFG trait, which may have implications for genetic studies when diagnosis is based on a single time-point measure.

    Original languageEnglish (US)
    Pages (from-to)2194-2202
    Number of pages9
    JournalDiabetologia
    Volume56
    Issue number10
    DOIs
    StatePublished - Oct 2013

    Keywords

    • Heritability
    • Impaired fasting glucose
    • Single nucleotide polymorphisms
    • Type 2 diabetes

    ASJC Scopus subject areas

    • Internal Medicine
    • Endocrinology, Diabetes and Metabolism

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