Genetic and phenotypic correlations between surrogate measures of insulin release obtained from OGTT data

Anette P Gjesing, Rasmus Ribel-Madsen, Marie N Harder, Hans Eiberg, Niels Grarup, Torben Jørgensen, Claus Thorn Ekstrøm, Oluf Pedersen, Torben Hansen

    5 Citationer (Scopus)

    Abstract

    AIMS/HYPOTHESIS: We examined the extent to which surrogate measures of insulin release have shared genetic causes.

    METHODS: Genetic and phenotypic correlations were calculated in a family cohort (n = 315) in which beta cell indices were estimated based on fasting and oral glucose-stimulated plasma glucose, serum C-peptide and serum insulin levels. Furthermore, we genotyped a large population-based cohort (n = 6,269) for common genetic variants known to associate with type 2 diabetes, fasting plasma glucose levels or fasting serum insulin levels to examine their association with various indices.

    RESULTS: We found a notable difference between the phenotypic and genetic correlations for the traits, emphasising that the phenotypic correlation is an insufficient measure of the magnitude of shared genetic impact. In addition, we found that corrected insulin response, insulinogenic index and incAUC for insulin after an oral glucose challenge shared the majority of their genetic backgrounds, with genetic correlations of 0.80-0.99. The BIGTT index for acute insulin response differed slightly more from the latter with genetic correlations of 0.78-0.87. The HOMA for beta cell function was genetically closely related to fasting insulin with a genetic correlation of 0.85. The effects of 82 selected susceptibility single nucleotide polymorphisms on these insulin secretion indices supported our interpretation of the data and added insight into the biological differences between the examined traits.

    CONCLUSIONS/INTERPRETATION: The level of shared genetic background varies between surrogate measures of insulin release, and this should be considered when designing a genetic association study to best obtain information on various mechanisms of insulin release.

    OriginalsprogEngelsk
    TidsskriftDiabetologia
    Vol/bind58
    Udgave nummer5
    Sider (fra-til)1006-12
    ISSN0012-186X
    DOI
    StatusUdgivet - 9 feb. 2015

    Fingeraftryk

    Dyk ned i forskningsemnerne om 'Genetic and phenotypic correlations between surrogate measures of insulin release obtained from OGTT data'. Sammen danner de et unikt fingeraftryk.

    Citationsformater