title: Variants associated with type 2 diabetes identified by the transethnic meta-analysis study: assessment in American Indians and evidence for a new signal in LPP.
abstract: OBJECTIVE
  A recent genome-wide trans-ancestry meta-analysis identified seven new loci associated with type 2 diabetes. We assessed the replication of the seven lead single nucleotide polymorphisms (SNPs) and evaluated these loci for additional signals in American Indians.
  
  
  METHODS
  Seven SNPs were genotyped in 7,710 individuals from a longitudinally studied American Indian population, and associations with type 2 diabetes, BMI and related phenotypes were assessed. Previous genome-wide association study (GWAS) data from these individuals were used to screen for additional type 2 diabetes signals at these loci. A variant independent of the trans-ancestry meta-analysis was identified within LPP, and its replication was assessed in an additional 3,106 urban American Indians.
  
  
  RESULTS
  SNP rs6813195 near to TMEM154 was nominally associated with type 2 diabetes (p = 0.01, OR 1.12 [95% CI 1.03, 1.22]) and adiposity: the type 2 diabetes risk allele was associated with a lower percentage body fat (β = -1.451%, p = 4.8 × 10(-4)). Another SNP, rs3130501 near to POU5F1-TCF19, was associated with BMI (β = -0.012, p = 0.004), type 2 diabetes adjusted for BMI (p = 0.02, OR 1.11 [95% CI 1.02, 1.22]), 2 h glucose concentrations (β = 0.080 mmol/l, p = 0.02) and insulin resistance estimated by homeostatic model (β = 0.039, p = 0.009). The independent variant identified at the LPP locus in our American Indian GWAS for type 2 diabetes was replicated in the additional samples (all American Indian meta-analysis, p = 8.9 × 10(-6), OR 1.29 [95% CI 1.15, 1.45]).
  
  
  CONCLUSIONS
  For two of the seven newly identified variants, there was nominal evidence for association with type 2 diabetes and related traits in American Indians. Identification of an independent variant at the LPP locus suggests the existence of more than one type 2 diabetes signal at this locus.
authors.affiliation: Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 445 North 5th Street, Phoenix, AZ, 85004, USA.
authors.forename: Anup K
authors.initials: AK
authors.lastname: Nair
authors.forename: Yunhua Li
authors.initials: YL
authors.lastname: Muller
authors.forename: Nellie A
authors.initials: NA
authors.lastname: McLean
authors.forename: Maryam
authors.initials: M
authors.lastname: Abdussamad
authors.forename: Paolo
authors.initials: P
authors.lastname: Piaggi
authors.forename: Sayuko
authors.initials: S
authors.lastname: Kobes
authors.forename: E Jennifer
authors.initials: EJ
authors.lastname: Weil
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Curtis
authors.forename: Robert G
authors.initials: RG
authors.lastname: Nelson
authors.forename: William C
authors.initials: WC
authors.lastname: Knowler
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hanson
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Baier
mesh_terms: D000328:Adult; D003598:Cytoskeletal Proteins / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D060588:LIM Domain Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D055815:Young Adult
chemical_list: D003598:Cytoskeletal Proteins; D060588:LIM Domain Proteins; C103594:LPP protein, human
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