title: Evaluation of DLG2 as a positional candidate for disposition index in African-Americans from the IRAS Family Study.
abstract: OBJECTIVE
  Evaluate discs large homolog 2 (DLG2) as a positional candidate gene for disposition index (DI) in the Insulin Resistance Atherosclerosis Family Study (IRAS-FS) African-American sample.
  
  
  METHODS
  SNPs (n=193) were selected for genotyping in 580 African-American individuals using a modified tagging algorithm. Follow-up genotyping was carried out within regions associated with DI. A subset of highly associated, uncorrelated SNPs was used as covariates in the linkage analysis to assess their contribution to linkage.
  
  
  RESULTS
  Evidence of association with DI was observed at the DLG2 locus (admixture-adjusted P=0.050-8.7 x 10(-5)) with additional signals observed in follow-up genotyping of 17 SNPs (P=0.033-0.0012). Inclusion of highly associated, uncorrelated SNPs as covariates in the linkage analysis explained linkage at the DLG2 locus (90.8 cM) and reduced the maximal LOD score (72.0 cM) from 4.37 to 3.71.
  
  
  CONCLUSIONS
  Evidence of association and an observed contribution to evidence for linkage to DI was observed for SNPs in DLG2 genotyped on the African-American individuals from the IRAS-FS. Although not the only gene in the region, these results suggest that variation at the DLG2 locus contributes to maintenance of glucose homeostasis through regulation of insulin sensitivity and beta-cell function as measured by DI.
authors.affiliation: Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Nicholette D
authors.initials: ND
authors.lastname: Palmer
authors.forename: Josyf C
authors.initials: JC
authors.lastname: Mychaleckyj
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Julie T
authors.initials: JT
authors.lastname: Ziegler
authors.forename: Adrienne H
authors.initials: AH
authors.lastname: Williams
authors.forename: Michael
authors.initials: M
authors.lastname: Bryer-Ash
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
mesh_terms: D000328:Adult; D000465:Algorithms; D044383:Black People / Q000235:genetics*; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002874:Chromosome Mapping; D005190:Family; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D051528:Guanylate Kinases / Q000235:genetics*; D006706:Homeostasis; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D001741:Black or African American
chemical_list: D001786:Blood Glucose; D025521:Tumor Suppressor Proteins; C496468:DLG2 protein, human; D051528:Guanylate Kinases; D005947:Glucose