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Vollenweider, P and Peltonen, L and Mooser, V and Sladek, R (2012) A genome-wide association search for type 2 diabetes genes in African Americans. PLoS One , 7 (1) , Article e29202 . 10.1371/journal.pone.0029202.
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African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
|Title:||A genome-wide association search for type 2 diabetes genes in African Americans.|
|Open access status:||An open access publication. A version is also available from UCL Discovery.|
|Additional information:||PMCID: PMC3251563 This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSC268200782096C. This work was supported by NIH grants K99 DK081350 (NDP), R01 DK066358 (DWB), R01 DK053591 (DWB), R01 HL56266 (BIF), R01 DK070941 (BIF) and in part by the General Clinical Research Center of the Wake Forest University School of Medicine grant M01 RR07122. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.|
|Keywords:||Adult, African Americans, Aged, Case-Control Studies, Cohort Studies, Diabetes Mellitus, Type 2, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Meta-Analysis as Topic, Middle Aged, Polymorphism, Single Nucleotide, Validation Studies as Topic|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science|
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health Care > Epidemiology and Public Health
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