Genome-wide linkage scans for type 2 diabetes mellitus in four ethnically diverse populations - Significant evidence for linkage on chromosome 4q in African Americans: The family investigation of nephropathy and diabetes research group

Alka Malhotra, Robert P. Igo, Farook Thameem, W. H.Linda Kao, Hanna E. Abboud, Sharon G. Adler, Nedal H. Arar, Donald W. Bowden, Ravindranath Duggirala, Barry I. Freedman, Katrina A.B. Goddard, Eli Ipp, Sudha K. Iyengar, Paul L. Kimmel, William C. Knowler, Orly Kohn, David Leehey, Lucy A. Meoni, Robert G. Nelson, Susanne B. NicholasRulan S. Parekh, Stephen S. Rich, Yii Der I. Chen, Mohammed F. Saad, Marina Scavini, Jeffrey R. Schelling, John R. Sedor, Vallabh O. Shah, Kent D. Taylor, Denyse Thornley-Brown, Philip G. Zager, Amanda Horvath, Robert L. Hanson

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Background: Previous studies have shown that in addition to environmental influences, type 2 diabetes mellitus (T2DM) has a strong genetic component. The goal of the current study is to identify regions of linkage for T2DM in ethnically diverse populations. Methods: Phenotypic and genotypic data were obtained from African American (AA; total number of individuals [N] = 1004), American Indian (AI; N = 883), European American (EA; N = 537), and Mexican American (MA; N = 1634) individuals from the Family Investigation of Nephropathy and Diabetes. Non-parametric linkage analysis, using an average of 4404 SNPs, was performed in relative pairs affected with T2DM in each ethnic group. In addition, family-based tests were performed to detect association with T2DM. Results: Statistically significant evidence for linkage was observed on chromosome 4q21.1 (LOD = 3.13; genome-wide p = 0.04) in AA. In addition, a total of 11 regions showed suggestive evidence for linkage (estimated at LOD > 1.71), with the highest LOD scores on chromosomes 12q21.31 (LOD = 2.02) and 22q12.3 (LOD = 2.38) in AA, 2p11.1 (LOD = 2.23) in AI, 6p12.3 (LOD = 2.77) in EA, and 13q21.1 (LOD =. 2.24) in MA. While no region overlapped across all ethnic groups, at least five loci showing LOD >1.71 have been identified in previously published studies. Conclusions: The results from this study provide evidence for the presence of genes affecting T2DM on chromosomes 4q, 12q, and 22q in AA; 6p in EA; 2p in AI; and 13q in MA. The strong evidence for linkage on chromosome 4q in AA provides important information given the paucity of diabetes genetic studies in this population.

Original languageEnglish (US)
Pages (from-to)740-747
Number of pages8
JournalDiabetes/Metabolism Research and Reviews
Volume25
Issue number8
DOIs
StatePublished - Nov 2009
Externally publishedYes

Keywords

  • Ethnicity
  • FIND
  • Linkage analysis
  • Type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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