Genome-Wide Association of CKD Progression: The Chronic Renal Insufficiency Cohort Study

Media type: E-Article
Title: Genome-Wide Association of CKD Progression: The Chronic Renal Insufficiency Cohort Study
Contributor: Parsa, Afshin; Kanetsky, Peter A.; Xiao, Rui; Gupta, Jayanta; Mitra, Nandita; Limou, Sophie; Xie, Dawei; Xu, Huichun; Anderson, Amanda Hyre; Ojo, Akinlolu; Kusek, John W.; Lora, Claudia M.; Hamm, L. Lee; He, Jiang; Sandholm, Niina; Jeff, Janina; Raj, Dominic E.; Böger, Carsten A.; Bottinger, Erwin; Salimi, Shabnam; Parekh, Rulan S.; Adler, Sharon G.; Langefeld, Carl D.; Bowden, Donald W.; [...]
Published: Ovid Technologies (Wolters Kluwer Health), 2017
Published in: Journal of the American Society of Nephrology, 28 (2017) 3, Seite 923-934
Language: English
DOI: 10.1681/asn.2015101152
ISSN: 1046-6673; 1533-3450
Keywords: Nephrology ; General Medicine
Origination:
Footnote:
Description: <jats:p>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 <jats:italic toggle="yes">P</jats:italic><1×10<jats:sup>−6</jats:sup> 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 <jats:italic toggle="yes">LINC00923</jats:italic> replicated in the African American Study of Kidney Disease and Hypertension cohort (discovery <jats:italic toggle="yes">P</jats:italic>=5.42×10<jats:sup>−7</jats:sup>; replication <jats:italic toggle="yes">P</jats:italic>=0.039; combined <jats:italic toggle="yes">P</jats:italic>=7.42×10<jats:sup>−9</jats:sup>). This SNP also associated with ESRD (hazard ratio, 2.0 (95% confidence interval, 1.5 to 2.7); <jats:italic toggle="yes">P</jats:italic>=4.90×10<jats:sup>−6</jats:sup>). Similarly, rs931891 in <jats:italic toggle="yes">LINC00923</jats:italic> associated with eGFR decline (<jats:italic toggle="yes">P</jats:italic>=1.44×10<jats:sup>−4</jats:sup>) in white patients without diabetes. In summary, SNPs in <jats:italic toggle="yes">LINC00923</jats:italic>, 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.</jats:p>
Access State: Open Access

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