Parsa, Afshin and Kanetsky, Peter A. and Xiao, Rui and Gupta, Jayanta and Mitra, Nandita and Limou, Sophie and Xie, Dawei and Xu, Huichun and Anderson, Amanda Hyre and Ojo, Akinlolu and Kusek, John W. and Lora, Claudia M. and Hamm, L. Lee and He, Jiang and Sandholm, Niina and Jeff, Janina and Raj, Dominic E. and Boeger, Carsten A. and Bottinger, Erwin and Salimi, Shabnam and Parekh, Rulan S. and Adler, Sharon G. and Langefeld, Carl D. and Bowden, Donald W. and Forsblom, Carol and Freedman, Barry I. and Lipkowitz, Michael and Fox, Caroline S. and Winkler, Cheryl A. and Feldman, Harold I. (2017) Genome-Wide Association of CKD Progression: The Chronic Renal Insufficiency Cohort Study. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 28 (3). pp. 923-934. ISSN 1046-6673, 1533-3450
Full text not available from this repository. (Request a copy)Abstract
The rate of decline of renal function varies significantly among individuals with CKD. To understand better the contribution of genetics to CKD progression, we performed a genome-wide association study among participants in the Chronic Renal Insufficiency Cohort Study. Our outcome of interest was CKD progression measured as change in eGFR over time among 1331 blacks and 1476 whites with CKD. We stratified all analyses by race and subsequently, diabetes status. Single-nucleotide polymorphisms (SNPs) that surpassed a significance threshold of P<1 x10(-6) for association with eGFR slope were selected as candidates for follow-up and secondarily tested for association with proteinuria and time to ESRD. We identified 12 such SNPs among black patients and six such SNPs among white patients. We were able to conduct follow-up analyses of three candidate SNPs in similar (replication) cohorts and eight candidate SNPs in phenotype-related (validation) cohorts. Among blacks without diabetes, rs653747 in LINC00923 replicated in the African American Study of Kidney Disease and Hypertension cohort (discovery P=5.42 x10(-7); replication P=0.039; combined P=7.42x 10(-9)). This SNP also associated with ESRD (hazard ratio, 2.0 (95% confidence interval, 1.5 to 2.7); P=4.90x10(-6)). Similarly, rs931891 in LINC00923 associated with eGFR decline (P=1.44 X 10(-4)) in white patients without diabetes. In summary, SNPs in LINC00923, an RNA gene expressed in the kidney, significantly associated with CKD progression in individuals with nondiabetic CKD. However, the lack of equivalent cohorts hampered replication for most discovery loci. Further replication of our findings in comparable study populations is warranted.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHRONIC KIDNEY-DISEASE; DIABETIC-NEPHROPATHY; DESIGN; GENES; HCARG; SET; PROTEINURIA; COMPONENTS; AMERICANS; VARIANTS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:01 |
| Last Modified: | 26 Feb 2019 12:16 |
| URI: | https://pred.uni-regensburg.de/id/eprint/338 |
Actions (login required)
 |
View Item |
