Uromodulin, the most abundant protein excreted in normal urine, plays major roles in kidney physiology and disease. The mechanisms regulating the urinary excretion of uromodulin remain essentially unknown. We conducted a meta-analysis of genome-wide association studies for raw (uUMOD) and indexed to creatinine (uUCR) urinary levels of uromodulin in 29,512 individuals of European ancestry from 13 cohorts. We tested whether variants in disease-causing genes associate with uromodulin levels and investigated the effects of keratin-40 (KRT40) on uromodulin processing. Results: Two genome-wide significant signals were identified for uUMOD: A novel locus (P 1.24E-08) over the KRT40 gene coding for KRT40, a type1 keratin expressed in the kidney, and the UMOD-PDILT locus (P 2.17E-88), which included two independent sets of SNPs spread over UMOD and PDILT. The meta-GWAS for uUCR yielded two genome-wide significant signals on the UMOD-PDILT locus and at the novel WDR72 locus previously associated with kidney function, urine pH and risk of kidney stones.
Joseph, Christina; Hayward, Caroline. (2021). Data pertaining to publication: Meta-GWAS Reveals Novel Genetic Variants Associated with Urinary Excretion of Uromodulin, 2003-2020 [dataset]. University of Edinburgh. Institute of Genetics and Cancer. MRC Human Genetics Unit. https://doi.org/10.7488/ds/3012.
|Date made available||6 Apr 2021|
|Temporal coverage||2003 - 2020|
|Geographical coverage||UNITED KINGDOM,CA,CANADA,HR,CROATIA,DE,GERMANY,SWITZERLAND,US,UNITED STATES,CH,UK|