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.
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.
Authors: M Trombetta; S Bonetti; M L Boselli; R Miccoli; E Trabetti; G Malerba; P F Pignatti; E Bonora; S Del Prato; R C Bonadonna Journal: Acta Diabetol Date: 2012-11-17 Impact factor: 4.280
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Authors: Andrew R Wood; Anna Jonsson; Anne U Jackson; Nan Wang; Nienke van Leewen; Nicholette D Palmer; Sayuko Kobes; Joris Deelen; Lorena Boquete-Vilarino; Jussi Paananen; Alena Stančáková; Dorret I Boomsma; Eco J C de Geus; Elisabeth M W Eekhoff; Andreas Fritsche; Mark Kramer; Giel Nijpels; Annemarie Simonis-Bik; Timon W van Haeften; Anubha Mahajan; Michael Boehnke; Richard N Bergman; Jaakko Tuomilehto; Francis S Collins; Karen L Mohlke; Karina Banasik; Christopher J Groves; Mark I McCarthy; Ewan R Pearson; Andrea Natali; Andrea Mari; Thomas A Buchanan; Kent D Taylor; Anny H Xiang; Anette P Gjesing; Niels Grarup; Hans Eiberg; Oluf Pedersen; Yii-Derr Chen; Markku Laakso; Jill M Norris; Ulf Smith; Lynne E Wagenknecht; Leslie Baier; Donald W Bowden; Torben Hansen; Mark Walker; Richard M Watanabe; Leen M 't Hart; Robert L Hanson; Timothy M Frayling Journal: Diabetes Date: 2017-05-10 Impact factor: 9.461