Journal article
Exome-based rare-variant analyses in CKD
S Cameron-Christie, CJ Wolock, E Groopman, S Petrovski, S Kamalakaran, G Povysil, D Vitsios, M Zhang, J Fleckner, RE March, S Gelfman, M Marasa, Y Li, S Sanna-Cherchi, K Kiryluk, AS Allen, BC Fellström, C Haefliger, A Platt, DB Goldstein Show all
Journal of the American Society of Nephrology | AMER SOC NEPHROLOGY | Published : 2019
Abstract
Background Studies have identified many common genetic associations that influence renal function and all-cause CKD, but these explain only a small fraction of variance in these traits. The contribution of rare variants has not been systematically examined. Methods We performed exome sequencing of 3150 individuals, who collectively encompassed diverse CKD subtypes, and 9563 controls. To detect causal genes and evaluate the contribution of rare variants we used collapsing analysis, in which we compared the proportion of cases and controls carrying rare variants per gene. Results The analyses captured five established monogenic causes of CKD: variants in PKD1, PKD2, and COL4A5 achieved study-w..
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Awarded by National Institutes of Health
Funding Acknowledgements
The study was supported by R01-MD009223 (to Dr. Gharavi) and the Institute of Genomic Medicine and the Columbia Precision Medicine Initiative. Dr. Groopman is supported by the National Institutes of Health grant 1F30DK116473. Dr. Cameron-Christie is a fellow of the AstraZeneca postdoctorate program, and reports other from Innovative Medicines and Early Development (IMED) Biotech Unit, AstraZeneca, during the conduct of the study; other from IMED Biotech Unit, AstraZeneca, outside the submitted work. Dr. Groopman reports grants from National Institutes of Health (grant number: 1F30DK116473-01), during the conduct of the study. Dr. Petrovski reports personal fees from AstraZeneca, during the conduct of the study. Dr. Povysil reports grants from AstraZeneca, during the conduct of the study; grants from AstraZeneca, outside the submitted work. Dr. Fleckner reports personal fees from AstraZeneca, personal fees from Novo Nordisk, outside the submitted work. Dr. March reports personal fees and other from AstraZeneca, outside the submitted work. Dr. Allen reports personal fees from AstraZeneca, during the conduct of the study; personal fees fromAstraZeneca, outside the submitted work. Dr. Fellstrom reports grants and personal fees from Pharmalink/Calliditas, personal fees from Alexion, grants from Bristol Meyers Squibb, other from Sandoz Pharmaceutical, outside the submitted work. Dr. Haefliger reports personal fees from AstraZeneca, during the conduct of the study; personal fees from AstraZeneca, outside the submitted work. Dr. Platt reports personal fees from AstraZeneca, during the conduct of the study; personal fees fromAstraZeneca, outside the submitted work. Dr. Goldstein reports personal fees from AstraZeneca, during the conduct of the study; other from Pairnomix, other from Praxis Therapeutics, other from Apostle Inc. outside the submitted work. Dr. Gharavi reports receiving research grants fromthe National Institutes of Health and the Renal Research Institute.