Additional Data pertaining to publication: Meta-GWAS Reveals Novel Genetic Variants Associated with Urinary Excretion of Uromodulin

Additional Data pertaining to publication: Meta-GWAS Reveals Novel Genetic Variants Associated with Urinary Excretion of Uromodulin 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.