Biology Faculty Articles

Authors

Sudha K. Iyengar, Case Western University
John R. Sedor, Case Western University
Barry I. Freedman, Wake Forest University
W. H. Linda Kao, Johns Hopkins University
Matthias Kretzler, University of Michigan - Ann Arbor
Benjamin J. Keller, University of Michigan - Ann Arbor
Hanna E. Abboud, University of Texas - San Antonio
Sharon G. Adler, Harbor-UCLA Medical Center
Lyle G. Best, Missouri Breaks Industries Research
Donald W. Bowden, Wake Forest University
Allison Burlock, University of Michigan - Ann Arbor
Yii-Der Ida Chen, Harbor-UCLA Medical Center
Shelley A. Cole, Texas Biomedical Research Institute
Mary E. Comeau, Wake Forest University
Jeffrey M. Curtis, National Institutes of Diabetes and Digestive and Kidney Diseases
Jasmin DIvers, Wake Forest University
Christiane Drechsler, University Hospital Würzburg - Germany
Ravi Duggirala, Texas Biomedical Research Institute
Robert C. Elston, Case Western University
Xiuqing Guo, Harbor-UCLA Medical Center
Huateng Huang, University of Michigan - Ann Arbor
Michael M. Hoffmann, University Medical Center - Freiburg, Germany
Barbara V. Howard, MedStar Health Research Institute
Eli Ipp, Harbor-UCLA Medical Center
Paul L. Kimmel, National Institute of Diabetes and Digestive and Kidney Diseases
Michael J. Klag, Johns Hopkins University
William C. Knowler, National Institutes of Diabetes and Digestive and Kidney Diseases
Orly F. Kohn, University of Chicago
Tennille S. Leak, University of Michigan - Ann Arbor
David J. Leehey, Loyola University - Chicago
Man Li, Johns Hopkins University
Alka Malhotra, National Institutes of Diabetes and Digestive and Kidney Diseases
Winfried Marz, University of Graz - Austria
Viji Nair, University of Michigan - Ann Arbor
Robert G. Nelson, National Institutes of Diabetes and Digestive and Kidney Diseases
Susanne B. Nicholas, University of California - Los Angeles
Stephen J. O'Brien, St. Petersburg State University - RussiaFollow
Madeleine V. Pahl, University of California - Irvine
Rulan S. Parekh, Hospital for Sick Children - Toronto, Canada; University of Toronto - Canada
Marcus G. Pezzolesi, Harvard University
Rebekah S. Rasooly, National Institute of Diabetes and Digestive Disease
Charles N. Rotimi, Center for Research on Genomics and Global Health
Jerome I. Rotter, Harbor-UCLA Medical Center
Jeffrey R. Schelling, Case Western University
Michael F. Seldin, University of California - Davis
Vallabh O. Shah, University of New Mexico - Albuquerque
Adam M. Smiles, Joslin Diabetes Center
Michael W. Smith, National Human Genome Research Institute
Kent D. Taylor, Harbor-UCLA Medical Center
Farook Thameem, University of Texas - San Antonio
Denyse P. Thornley-Brown, University of Alabama - Birmingham
Barbara J. Truitt, Case Western University
Christoph Wanner, University Hospital Wurzburg - Germany
E. Jennifer Weil, National Institutes of Diabetes and Digestive and Kidney Diseases
Cheryl Winkler, National Cancer Institute at Frederick
Philip G. Zager, University of New Mexico - Albuquerque
Robert P. Igo Jr., Case Western University
Robert L. Hanson, National Institutes of Diabetes and Digestive and Kidney Diseases
Carl D. Langefeld, Harbor-UCLA Medical Center
Family Investigation of Nephropathy and Diabetes (FIND) Research Group

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.

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.

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

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015

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