title: Insulin sensitivity and insulin clearance are heritable and have strong genetic correlation in Mexican Americans.
abstract: OBJECTIVE
  The GUARDIAN (Genetics UndeRlying DIAbetes in HispaNics) consortium is described, along with heritability estimates and genetic and environmental correlations of insulin sensitivity and metabolic clearance rate of insulin (MCRI).
  
  
  METHODS
  GUARDIAN is comprised of seven cohorts, consisting of 4,336 Mexican-American individuals in 1,346 pedigrees. Insulin sensitivity (SI ), MCRI, and acute insulin response (AIRg) were measured by frequently sampled intravenous glucose tolerance test in four cohorts. Insulin sensitivity (M, M/I) and MCRI were measured by hyperinsulinemic-euglycemic clamp in three cohorts. Heritability and genetic and environmental correlations were estimated within the family cohorts (totaling 3,925 individuals) using variance components.
  
  
  RESULTS
  Across studies, age, and gender-adjusted heritability of insulin sensitivity (SI , M, M/I) ranged from 0.23 to 0.48 and of MCRI from 0.35 to 0.73. The ranges for the genetic correlations were 0.91 to 0.93 between SI and MCRI; and -0.57 to -0.59 for AIRg and MCRI (all P < 0.0001). The ranges for the environmental correlations were 0.54 to 0.74 for SI and MCRI (all P < 0.0001); and -0.16 to -0.36 for AIRg and MCRI (P < 0.0001-0.06).
  
  
  CONCLUSIONS
  These data support a strong familial basis for insulin sensitivity and MCRI in Mexican Americans. The strong genetic correlations between MCRI and SI suggest common genetic determinants.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA; Medical Genetics Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Mark O
authors.initials: MO
authors.lastname: Goodarzi
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Anny H
authors.initials: AH
authors.lastname: Xiang
authors.forename: Yii-Der I
authors.initials: YD
authors.lastname: Chen
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Guo
authors.forename: Anthony J G
authors.initials: AJ
authors.lastname: Hanley
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Raffel
authors.forename: Fouad
authors.initials: F
authors.lastname: Kandeel
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Nadler
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchanan
authors.forename: Jill M
authors.initials: JM
authors.lastname: Norris
authors.forename: Tasha E
authors.initials: TE
authors.lastname: Fingerlin
authors.forename: Carlos
authors.initials: C
authors.lastname: Lorenzo
authors.forename: Marian J
authors.initials: MJ
authors.lastname: Rewers
authors.forename: Steven M
authors.initials: SM
authors.lastname: Haffner
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.forename: Richard N
authors.initials: RN
authors.lastname: Bergman
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Richard M
authors.initials: RM
authors.lastname: Watanabe
authors.forename: Lynne E
authors.initials: LE
authors.lastname: Wagenknecht
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003120:Colorado; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008657:Metabolic Clearance Rate / Q000235:genetics*; D017058:Mexican Americans / Q000235:genetics*; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D012189:Retrospective Studies; D013781:Texas
chemical_list: D007328:Insulin