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Genome-wide association study identifies novel loci for type 2 diabetes-attributed end-stage kidney disease in African Americans.

ABSTRACT: BACKGROUND:End-stage kidney disease (ESKD) is a significant public health concern disproportionately affecting African Americans (AAs). Type 2 diabetes (T2D) is the leading cause of ESKD in the USA, and efforts to uncover genetic susceptibility to diabetic kidney disease (DKD) have had limited success. A prior genome-wide association study (GWAS) in AAs with T2D-ESKD was expanded with additional AA cases and controls and genotypes imputed to the higher density 1000 Genomes reference panel. The discovery analysis included 3432 T2D-ESKD cases and 6977 non-diabetic non-nephropathy controls (N?=?10,409), followed by a discrimination analysis in 2756 T2D non-nephropathy controls to exclude T2D-associated variants. RESULTS:Six independent variants located in or near RND3/RBM43, SLITRK3, ENPP7, GNG7, and APOL1 achieved genome-wide significant association (P?

SUBMITTER: Guan M

PROVIDER: S-EPMC6521376 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Genome-wide association study identifies novel loci for type 2 diabetes-attributed end-stage kidney disease in African Americans.

Guan Meijian M Keaton Jacob M JM Dimitrov Latchezar L Hicks Pamela J PJ Xu Jianzhao J Palmer Nicholette D ND Ma Lijun L Das Swapan K SK Chen Yii-Der I YI Coresh Josef J Fornage Myriam M Franceschini Nora N Kramer Holly H Langefeld Carl D CD Mychaleckyj Josyf C JC Parekh Rulan S RS Post Wendy S WS Rasmussen-Torvik Laura J LJ Rich Stephen S SS Rotter Jerome I JI Sedor John R JR Thornley-Brown Denyse D Tin Adrienne A Wilson James G JG Freedman Barry I BI Bowden Donald W DW Ng Maggie C Y MCY

Human genomics 20190515 1

<h4>Background</h4>End-stage kidney disease (ESKD) is a significant public health concern disproportionately affecting African Americans (AAs). Type 2 diabetes (T2D) is the leading cause of ESKD in the USA, and efforts to uncover genetic susceptibility to diabetic kidney disease (DKD) have had limited success. A prior genome-wide association study (GWAS) in AAs with T2D-ESKD was expanded with additional AA cases and controls and genotypes imputed to the higher density 1000 Genomes reference pane ...[more]

PMID: 31092297

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Project description:Background & aimsThe inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn's disease (CD) cause significant morbidity and are increasing in prevalence among all populations, including African Americans. More than 200 susceptibility loci have been identified in populations of predominantly European ancestry, but few loci have been associated with IBD in other ethnicities.MethodsWe performed 2 high-density, genome-wide scans comprising 2345 cases of African Americans with IBD (1646 with CD, 583 with UC, and 116 inflammatory bowel disease unclassified) and 5002 individuals without IBD (controls, identified from the Health Retirement Study and Kaiser Permanente database). Single-nucleotide polymorphisms (SNPs) associated at P < 5.0 × 10-8 in meta-analysis with a nominal evidence (P < .05) in each scan were considered to have genome-wide significance.ResultsWe detected SNPs at HLA-DRB1, and African-specific SNPs at ZNF649 and LSAMP, with associations of genome-wide significance for UC. We detected SNPs at USP25 with associations of genome-wide significance for IBD. No associations of genome-wide significance were detected for CD. In addition, 9 genes previously associated with IBD contained SNPs with significant evidence for replication (P < 1.6 × 10-6): ADCY3, CXCR6, HLA-DRB1 to HLA-DQA1 (genome-wide significance on conditioning), IL12B,PTGER4, and TNC for IBD; IL23R, PTGER4, and SNX20 (in strong linkage disequilibrium with NOD2) for CD; and KCNQ2 (near TNFRSF6B) for UC. Several of these genes, such as TNC (near TNFSF15), CXCR6, and genes associated with IBD at the HLA locus, contained SNPs with unique association patterns with African-specific alleles.ConclusionsWe performed a genome-wide association study of African Americans with IBD and identified loci associated with UC in only this population; we also replicated IBD, CD, and UC loci identified in European populations. The detection of variants associated with IBD risk in only people of African descent demonstrates the importance of studying the genetics of IBD and other complex diseases in populations beyond those of European ancestry.

Dataset Information

Genome-wide association study identifies novel loci for type 2 diabetes-attributed end-stage kidney disease in African Americans.

Publications

Genome-wide association study identifies novel loci for type 2 diabetes-attributed end-stage kidney disease in African Americans.

Similar Datasets

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