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Identification of 22 novel loci associated with urinary biomarkers of albumin, sodium, and potassium excretion
Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, 300 Pasteur Dr,Mail Code 5406, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.ORCID iD: 0000-0001-5894-0351
Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, 300 Pasteur Dr,Mail Code 5406, Stanford, CA 94305 USA.
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2019 (English)In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 95, no 5, p. 1197-1208Article in journal (Refereed) Published
Abstract [en]

Urine biomarkers reflecting kidney function and handling of dietary sodium and potassium are strongly associated with several common diseases including chronic kidney disease, cardiovascular disease, and diabetes mellitus. Knowledge about the genetic determinants of these biomarkers may shed light on pathophysiological mechanisms underlying the development of these diseases. We performed genome-wide association studies of urinary albumin: creatinine ratio (UACR), urinary potassium: creatinine ratio (UK/UCr), urinary sodium: creatinine ratio (UNa/UCr) and urinary sodium: potassium ratio (UNa/UK) in up to 218,450 (discovery) and 109,166 (replication) unrelated individuals of European ancestry from the UK Biobank. Further, we explored genetic correlations, tissue-specific gene expression, and possible genes implicated in the regulation of these biomarkers. After replication, we identified 19 genome-wide significant independent loci associated with UACR, 6 each with UK/UCr and UNa/UCr, and 4 with UNa/UK. In addition to 22 novel associations, we confirmed several established associations, including between the CUBN locus and microalbuminuria. We detected high pairwise genetic correlation across the urinary biomarkers, and between their levels and several physiological measurements. We highlight GIPR, a potential diabetes drug target, as possibly implicated in the genetic control of urinary potassium excretion, and NRBP1, a locus associated with gout, as plausibly involved in sodium and albumin excretion. Overall, we identified 22 novel genome-wide significant associations with urinary biomarkers and confirmed several previously established associations, providing new insights into the genetic basis of these traits and their connection to chronic diseases.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC , 2019. Vol. 95, no 5, p. 1197-1208
Keywords [en]
chronic kidney disease, genetics, microalbuminuria, urinary biomarkers
National Category
Urology and Nephrology
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URN: urn:nbn:se:uu:diva-383153DOI: 10.1016/j.kint.2018.12.017ISI: 000465213400023PubMedID: 30910378OAI: oai:DiVA.org:uu-383153DiVA, id: diva2:1315067
Available from: 2019-05-10 Created: 2019-05-10 Last updated: 2019-05-10Bibliographically approved

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