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Diabetes Metab Res Rev. 2009 Nov;25(8):740-7. doi: 10.1002/dmrr.1031.

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.

Diabetes/metabolism research and reviews

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 Nicholas, Rulan 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,

Affiliations

  1. National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona, USA.

PMID: 19795399 PMCID: PMC2783577 DOI: 10.1002/dmrr.1031

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.

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