Biology Faculty Articles
Document Type
Article
Publication Date
8-25-2015
Publication Title
PLoS Genetics
ISSN
1553-7390
Volume
11
Issue/No.
8 e1005352
First Page
1
Last Page
19
Abstract
Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10-9). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10-8), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD.
Additional Comments
National Institute of Diabetes and Digestive and Kidney Diseases grant #s: U01DK57292, U01DK57329, U01DK057300, U01DK057298, U01DK057249, U01DK57295, U01DK070657, U01DK057303, U01DK57304; National Heart, Lung and Blood Institute grant #s: U01HL065520, U01HL041654, U01HL041652; National Cancer Institute contract #: N01-CO-12400; National Center for Research Resources for the General Clinical Research Center grant #s: M01-RR-000080, M01-RR-07122, M01-RR-00425, M01-RR-00827–29, HSC M01-RR-00997, M01-RR-01346
NSUWorks Citation
Iyengar, Sudha K.; John R. Sedor; Barry I. Freedman; W. H. Linda Kao; Matthias Kretzler; Benjamin J. Keller; Hanna E. Abboud; Sharon G. Adler; Lyle G. Best; Donald W. Bowden; Allison Burlock; Yii-Der Ida Chen; Shelley A. Cole; Mary E. Comeau; Jeffrey M. Curtis; Jasmin DIvers; Christiane Drechsler; Ravi Duggirala; Robert C. Elston; Xiuqing Guo; Huateng Huang; Michael M. Hoffmann; Barbara V. Howard; Eli Ipp; Paul L. Kimmel; Michael J. Klag; William C. Knowler; Orly F. Kohn; Tennille S. Leak; David J. Leehey; Man Li; Alka Malhotra; Winfried Marz; Viji Nair; Robert G. Nelson; Susanne B. Nicholas; Stephen J. O'Brien; Madeleine V. Pahl; Rulan S. Parekh; Marcus G. Pezzolesi; Rebekah S. Rasooly; Charles N. Rotimi; Jerome I. Rotter; Jeffrey R. Schelling; Michael F. Seldin; Vallabh O. Shah; Adam M. Smiles; Michael W. Smith; Kent D. Taylor; Farook Thameem; Denyse P. Thornley-Brown; Barbara J. Truitt; Christoph Wanner; E. Jennifer Weil; Cheryl Winkler; Philip G. Zager; Robert P. Igo Jr.; Robert L. Hanson; Carl D. Langefeld; and Family Investigation of Nephropathy and Diabetes (FIND) Research Group. 2015. "Genome-Wide Association and Trans-ethnic Meta-Analysis for Advanced Diabetic Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND)." PLoS Genetics 11, (8 e1005352): 1-19. https://nsuworks.nova.edu/cnso_bio_facarticles/732
ORCID ID
0000-0001-7353-8301
ResearcherID
N-1726-2015
Comments
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.