DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Microalbuminuria. The EFO term Microalbuminuria was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: Microalbuminuria

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

A Teumer, A Tin, R Sorice, M Gorski, NC Yeo, AY Chu, M Li, Y Li, V Mijatovic, YA Ko, D Taliun, A Luciani, MH Chen, Q Yang, MC Foster, M Olden, LT Hiraki, BO Tayo, C Fuchsberger, AK Dieffenbach, AR Shuldiner, AV Smith, AM Zappa, A Lupo, B Kollerits, B Ponte, B Stengel, BK Krämer, B Paulweber, BD Mitchell, C Hayward, C Helmer, C Meisinger, C Gieger, CM Shaffer, C Müller, C Langenberg, D Ackermann, D Siscovick, E Boerwinkle, F Kronenberg, GB Ehret, G Homuth, G Waeber, G Navis, G Gambaro, G Malerba, G Eiriksdottir, G Li, HE Wichmann, H Grallert, H Wallaschofski, H Völzke, H Brenner, H Kramer, I Mateo Leach, I Rudan, HL Hillege, JS Beckmann, JC Lambert, J Luan, JH Zhao, J Chalmers, J Coresh, JC Denny, K Butterbach, LJ Launer, L Ferrucci, L Kedenko, M Haun, M Metzger, M Woodward, MJ Hoffman, M Nauck, M Waldenberger, M Pruijm, M Bochud, M Rheinberger, N Verweij, NJ Wareham, N Endlich, N Soranzo, O Polasek, P van der Harst, PP Pramstaller, P Vollenweider, PS Wild, RT Gansevoort, R Rettig, R Biffar, RJ Carroll, R Katz, RJ Loos, SJ Hwang, S Coassin, S Bergmann, SE Rosas, S Stracke, TB Harris, T Corre, T Zeller, T Illig, T Aspelund, T Tanaka, U Lendeckel, U Völker, V Gudnason, V Chouraki, W Koenig, Z Kutalik, JR O'Connell, A Parsa, IM Heid, AD Paterson, IH de Boer, O Devuyst, J Lazar, K Endlich, K Susztak, J Tremblay, P Hamet, HJ Jacob, CA Böger, CS Fox, C Pattaro, A Köttgen

TITLE:

Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes.

JOURNAL:

Diabetes Mar 2016, Vol 65, pp. 803-17

ABSTRACT:

Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.4 × 10(-10)). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. Single nucleotide polymorphisms at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in the average UACR per minor allele was 21% for HS6ST1 (P = 6.3 × 10(-7)) and 13% for RAB38/CTSC (P = 5.8 × 10(-7)). Experiments using streptozotocin-induced diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout versus control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared with control subjects. The loci identified here confirm known pathways and highlight novel pathways influencing albuminuria. PUBMED: 26631737
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