| Contributors: |
Olden, M; Corre, T; Hayward, C; Toniolo, D; Ulivi, S; Gasparini, P; Pistis, G; Hwang, Sj; Bergmann, S; Campbell, H; Cocca, M; Gandin, I; Girotto, G; Glaudemans, B; Hastie, Nd; Loffing, J; Polasek, O; Rampoldi, L; Rudan, I; Sala, C; Traglia, M; Vollenweider, P; Vuckovic, D; Youhanna, S; Weber, J; Wright, Af; Kutalik, Z; Bochud, M; Fox, C; Devuyst, O |
| Description: |
Uromodulin is expressed exclusively in the thick ascending limb and is the most abundant protein excreted in normal urine. Variants in UMOD, which encodes uromodulin, are associated with renal function, and urinary uromodulin levels may be a biomarker for kidney disease. However, the genetic factors regulating uromodulin excretion are unknown. We conducted a meta-analysis of urinary uromodulin levels to identify associated common genetic variants in the general population. We included 10,884 individuals of European descent from three genetic isolates and three urban cohorts. Each study measured uromodulin indexed to creatinine and conducted linear regression analysis of approximately 2.5 million single nucleotide polymorphisms using an additive model. We also tested whether variants in genes expressed in the thick ascending limb associate with uromodulin levels. rs12917707, located near UMOD and previously associated with renal function and CKD, had the strongest association with urinary uromodulin levels (P |