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 End-stage renal disease in Type 1 diabetics. The EFO term type I diabetes mellitus, chronic kidney disease 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: type I diabetes mellitus, chronic kidney disease

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

N Sandholm, AJ McKnight, RM Salem, EP Brennan, C Forsblom, V Harjutsalo, VP Mäkinen, GJ McKay, DM Sadlier, WW Williams, F Martin, NM Panduru, L Tarnow, J Tuomilehto, K Tryggvason, G Zerbini, ME Comeau, CD Langefeld, C Godson, JN Hirschhorn, AP Maxwell, JC Florez, PH Groop

TITLE:

Chromosome 2q31.1 associates with ESRD in women with type 1 diabetes.

JOURNAL:

Journal of the American Society of Nephrology : JASN Oct 2013, Vol 24, pp. 1537-43

ABSTRACT:

Sex and genetic variation influence the risk of developing diabetic nephropathy and ESRD in patients with type 1 diabetes. We performed a genome-wide association study in a cohort of 3652 patients from the Finnish Diabetic Nephropathy (FinnDiane) Study with type 1 diabetes to determine whether sex-specific genetic risk factors for ESRD exist. A common variant, rs4972593 on chromosome 2q31.1, was associated with ESRD in women (P<5×10(-8)) but not in men (P=0.77). This association was replicated in the meta-analysis of three independent type 1 diabetes cohorts (P=0.02) and remained significant for women (P<5×10(-8); odds ratio, 1.81 [95% confidence interval, 1.47 to 2.24]) upon combined meta-analysis of the discovery and replication cohorts. rs4972593 is located between the genes that code for the Sp3 transcription factor, which interacts directly with estrogen receptor α and regulates the expression of genes linked to glomerular function and the pathogenesis of nephropathy, and the CDCA7 transcription factor, which regulates cell proliferation. Further examination revealed potential transcription factor-binding sites within rs4972593 and predicted eight estrogen-responsive elements within 5 kb of this locus. Moreover, we found sex-specific differences in the glomerular expression levels of SP3 (P=0.004). Overall, these results suggest that rs4972593 is a sex-specific genetic variant associated with ESRD in patients with type 1 diabetes and may underlie the sex-specific protection against ESRD. PUBMED: 24029427
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