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Haplotype association analysis of genes within the WNT signalling pathways in diabetic nephropathy.


ABSTRACT: Renal interstitial fibrosis and glomerular sclerosis are hallmarks of diabetic nephropathy (DN) and several studies have implicated members of the WNT pathways in these pathological processes. This study comprehensively examined common genetic variation within the WNT pathway for association with DN.Genes within the WNT pathways were selected on the basis of nominal significance and consistent direction of effect in the GENIE meta-analysis dataset. Common SNPs and common haplotypes were examined within the selected WNT pathway genes in a white population with type 1 diabetes, discordant for DN (cases: n?=?718; controls: n?=?749). SNPs were genotyped using Sequenom or Taqman assays. Association analyses were performed using PLINK, to compare allele and haplotype frequencies in cases and controls. Correction for multiple testing was performed by either permutation testing or using false discovery rate.A logistic regression model including collection centre, duration of diabetes, and average HbA1c as covariates highlighted three SNPs in GSK3B (rs17810235, rs17471, rs334543), two in DAAM1 (rs1253192, rs1252906) and one in NFAT5 (rs17297207) as being significantly (P?

SUBMITTER: Kavanagh DH 

PROVIDER: S-EPMC3701522 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Haplotype association analysis of genes within the WNT signalling pathways in diabetic nephropathy.

Kavanagh David H DH   Savage David A DA   Patterson Christopher C CC   McKnight Amy Jayne AJ   Crean John K JK   Maxwell Alexander P AP   McKay Gareth J GJ  

BMC nephrology 20130618


<h4>Background</h4>Renal interstitial fibrosis and glomerular sclerosis are hallmarks of diabetic nephropathy (DN) and several studies have implicated members of the WNT pathways in these pathological processes. This study comprehensively examined common genetic variation within the WNT pathway for association with DN.<h4>Methods</h4>Genes within the WNT pathways were selected on the basis of nominal significance and consistent direction of effect in the GENIE meta-analysis dataset. Common SNPs  ...[more]

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