Benonisdottir, S;
Kristjansson, RP;
Oddsson, A;
Steinthorsdottir, V;
Mikaelsdottir, E;
Kehr, B;
Jensson, BO;
... Stefansson, K; + view all
(2019)
Sequence variants associating with urinary biomarkers.
Human Molecular Genetics
, 28
(7)
pp. 1199-1211.
10.1093/hmg/ddy409.
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Abstract
Urine dipstick tests are widely used in routine medical care to diagnose kidney and urinary tract and metabolic diseases. Several environmental factors are known to affect the test results, whereas the effects of genetic diversity are largely unknown. We tested 32.5 million sequence variants for association with urinary biomarkers in a set of 150 274 Icelanders with urine dipstick measurements. We detected 20 association signals, of which 14 are novel, associating with at least one of five clinical entities defined by the urine dipstick: glucosuria, ketonuria, proteinuria, hematuria and urine pH. These include three independent glucosuria variants at SLC5A2, the gene encoding the sodium-dependent glucose transporter (SGLT2), a protein targeted pharmacologically to increase urinary glucose excretion in the treatment of diabetes. Two variants associating with proteinuria are in LRP2 and CUBN, encoding the co-transporters megalin and cubilin, respectively, that mediate proximal tubule protein uptake. One of the hematuria-associated variants is a rare, previously unreported 2.5 kb exonic deletion in COL4A3. Of the four signals associated with urine pH, we note that the pH-increasing alleles of two variants (POU2AF1, WDR72) associate significantly with increased risk of kidney stones. Our results reveal that genetic factors affect variability in urinary biomarkers, in both a disease dependent and independent context.
| Type: | Article |
|---|---|
| Title: | Sequence variants associating with urinary biomarkers |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/hmg/ddy409 |
| Publisher version: | https://doi.org/10.1093/hmg/ddy409 |
| Language: | English |
| Additional information: | This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Genetics & Heredity, GENOME-WIDE ASSOCIATION, GENETIC ARCHITECTURE, MUTATIONS, MEGALIN, DISEASE, PATHOPHYSIOLOGY, HETEROGENEITY, MANAGEMENT, HEMATURIA, INSIGHTS |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10073044 |
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