Diabetes Research and Clinical Practice
Volume 87, Issue 1 , Pages 69-76, January 2010

Evaluation of DLG2 as a positional candidate for disposition index in African-Americans from the IRAS family study

  • Nicholette D. Palmer

      Affiliations

    • Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC, United States
    • Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, United States
    • Diabetes Research Center, Wake Forest University School of Medicine, Winston-Salem, NC, United States
  • ,
  • Josyf C. Mychaleckyj

      Affiliations

    • Center for Public Health Genomics, University of Virginia, Charlottesville, VA, United States
  • ,
  • Carl. D. Langefeld

      Affiliations

    • Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, United States
  • ,
  • Julie T. Ziegler

      Affiliations

    • Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, United States
  • ,
  • Adrienne. H. Williams

      Affiliations

    • Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, United States
  • ,
  • Michael. Bryer-Ash

      Affiliations

    • Section on Endocrinology and Diabetes, University of Oklahoma, Oklahoma City, OK, United States
  • ,
  • Donald. W. Bowden

      Affiliations

    • Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC, United States
    • Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, United States
    • Diabetes Research Center, Wake Forest University School of Medicine, Winston-Salem, NC, United States
    • Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, United States
    • Corresponding Author InformationCorresponding author at: Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157, United States. Tel.: +1 336 713 7500; fax: +1 336 713 7566.

Received 9 April 2009; received in revised form 23 September 2009; accepted 26 October 2009. published online 23 November 2009.

Abstract 

Aims

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=0.050–8.7×10−5) 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 (90.8cM) and reduced the maximal LOD score (72.0cM) 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 β-cell function as measured by DI.

Keywords: African-Americans, Glucose Homeostasis, Disposition Index, SNPs, Linkage, Association

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PII: S0168-8227(09)00463-X

doi:10.1016/j.diabres.2009.10.015

Diabetes Research and Clinical Practice
Volume 87, Issue 1 , Pages 69-76, January 2010