title: Genetic and phenotypic correlations between surrogate measures of insulin release obtained from OGTT data.
abstract: OBJECTIVE
  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
  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: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 1-3, DK-2100, Copenhagen, Denmark, Anette.Gjesing@sund.ku.dk.
authors: Anette P
authors: AP
authors: Gjesing
authors: Rasmus
authors: R
authors: Ribel-Madsen
authors: Marie N
authors: MN
authors: Harder
authors: Hans
authors: H
authors: Eiberg
authors: Niels
authors: N
authors: Grarup
authors: Torben
authors: T
authors: Jørgensen
authors: Claus T
authors: CT
authors: Ekstrøm
authors: Oluf
authors: O
authors: Pedersen
authors: Torben
authors: T
authors: Hansen
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D005215:Fasting; D005260:Female; D005838:Genotype; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000235:genetics*; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin