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Sequence variants associating with urinary biomarkers.

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.

SUBMITTER: Benonisdottir S

PROVIDER: S-EPMC6423415 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Sequence variants associating with urinary biomarkers.

Benonisdottir Stefania S Kristjansson Ragnar P RP Oddsson Asmundur A Steinthorsdottir Valgerdur V Mikaelsdottir Evgenia E Kehr Birte B Jensson Brynjar O BO Arnadottir Gudny A GA Sulem Gerald G Sveinbjornsson Gardar G Kristmundsdottir Snaedis S Ivarsdottir Erna V EV Tragante Vinicius V Gunnarsson Bjarni B Runolfsdottir Hrafnhildur Linnet HL Arthur Joseph G JG Deaton Aimee M AM Eyjolfsson Gudmundur I GI Davidsson Olafur B OB Asselbergs Folkert W FW Hreidarsson Astradur B AB Rafnar Thorunn T Thorleifsson Gudmar G Edvardsson Vidar V Sigurdsson Gunnar G Helgadottir Anna A Halldorsson Bjarni V BV Masson Gisli G Holm Hilma H Onundarson Pall T PT Indridason Olafur S OS Benediktsson Rafn R Palsson Runolfur R Gudbjartsson Daniel F DF Olafsson Isleifur I Thorsteinsdottir Unnur U Sulem Patrick P Stefansson Kari K

Human molecular genetics 20190401 7

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 clini ...[more]

PMID: 30476138

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Sequence variants associating with urinary biomarkers.

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Sequence variants associating with urinary biomarkers.

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