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

Research output: Contribution to journalJournal articleResearchpeer-review

Anette Marianne Prior Gjesing, Rasmus Ribel-Madsen, Marie Neergaard Harder, Hans Eiberg, Niels Grarup, Torben Jørgensen, Claus T Ekstrøm, Oluf Pedersen, Torben Hansen

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.

Original languageEnglish
JournalDiabetologia
Volume58
Issue number5
Pages (from-to)1006-1012
Number of pages7
ISSN0012-186X
DOIs
Publication statusPublished - May 2015

ID: 134748111