title: Epidemiology and genetic determinants of progressive deterioration of glycaemia in American Indians: the Strong Heart Family Study.
abstract: OBJECTIVE
  Type 2 diabetes is a chronic, heterogeneous disease and a major risk factor for cardiovascular diseases. The underlying mechanisms leading to progression to type 2 diabetes are not fully understood and genetic tools may help to identify important pathways of glycaemic deterioration.
  
  
  METHODS
  Using prospective data on American Indians from the Strong Heart Family Study, we identified 373 individuals defined as progressors (diabetes incident cases), 566 individuals with transitory impaired fasting glucose (IFG) and 1,011 controls (normal fasting glycaemia at all visits). We estimated the heritability (h(2)) of the traits and the evidence for association with 16 known variants identified in type 2 diabetes genome-wide association studies.
  
  
  RESULTS
  We noted high h(2) for diabetes progression (h(2) = 0.65 ± 0.16, p = 2.7 × 10(-6)) but little contribution of genetic factors to transitory IFG (h(2) = 0.09 ± 0.10, p = 0.19) for models adjusted for multiple risk factors. At least three variants (in WFS1, TSPAN8 and THADA) were nominally associated with diabetes progression in age- and sex-adjusted analyses with estimates showing the same direction of effects as reported in the discovery European ancestry studies.
  
  
  CONCLUSIONS
  Our findings do not exclude these loci for diabetes susceptibility in American Indians and suggest phenotypic heterogeneity of the IFG trait, which may have implications for genetic studies when diagnosis is based on a single time-point measure.
authors.affiliation: Department of Epidemiology, University of North Carolina, 137 E. Franklin St, Suite 306 CB No 8050, Chapel Hill, NC 27599-8050, USA. noraf@unc.edu
authors.forename: N
authors.initials: N
authors.lastname: Franceschini
authors.forename: K
authors.initials: K
authors.lastname: Haack
authors.forename: H H H
authors.initials: HH
authors.lastname: Göring
authors.forename: V S
authors.initials: VS
authors.lastname: Voruganti
authors.forename: S
authors.initials: S
authors.lastname: Laston
authors.forename: L
authors.initials: L
authors.lastname: Almasy
authors.forename: E T
authors.initials: ET
authors.lastname: Lee
authors.forename: L G
authors.initials: LG
authors.lastname: Best
authors.forename: R R
authors.initials: RR
authors.lastname: Fabsitz
authors.forename: K E
authors.initials: KE
authors.lastname: North
authors.forename: J W
authors.initials: JW
authors.lastname: Maccluer
authors.forename: J B
authors.initials: JB
authors.lastname: Meigs
authors.forename: J S
authors.initials: JS
authors.lastname: Pankow
authors.forename: S A
authors.initials: SA
authors.lastname: Cole
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis* / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000453:epidemiology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007198:Indians, North American; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D001786:Blood Glucose