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

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-Arnerican 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. (C) 2009 Elsevier Ireland Ltd. All rights reserved.