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

Hdl Handle:
http://hdl.handle.net/10147/295223
Title:
Haplotype association analysis of genes within the WNT signalling pathways in diabetic nephropathy
Authors:
Kavanagh, David H; Savage, David A; Patterson, Christopher C; McKnight, Amy J; Crean, John K; Maxwell, Alexander P; McKay, Gareth J; the Warren 3/UK GoKinD Study Group
Citation:
BMC Nephrology. 2013 Jun 18;14(1):126
Issue Date:
18-Jun-2013
URI:
http://dx.doi.org/10.1186/1471-2369-14-126; http://hdl.handle.net/10147/295223
Abstract:
Abstract Background 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. Methods 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. Results 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 < 0.05) associated with DN, however these SNPs did not remain significant after correction for multiple testing. Logistic regression of haplotypes, with ESRD as the outcome, and pairwise interaction analyses did not yield any significant results after correction for multiple testing. Conclusions These results indicate that both common SNPs and common haplotypes of WNT pathway genes are not strongly associated with DN. However, this does not completely exclude these or the WNT pathways from association with DN, as unidentified rare genetic or copy number variants could still contribute towards the genetic architecture of DN.
Item Type:
Journal Article

Full metadata record

DC FieldValue Language
dc.contributor.authorKavanagh, David H-
dc.contributor.authorSavage, David A-
dc.contributor.authorPatterson, Christopher C-
dc.contributor.authorMcKnight, Amy J-
dc.contributor.authorCrean, John K-
dc.contributor.authorMaxwell, Alexander P-
dc.contributor.authorMcKay, Gareth J-
dc.contributor.authorthe Warren 3/UK GoKinD Study Group-
dc.date.accessioned2013-07-04T12:49:38Z-
dc.date.available2013-07-04T12:49:38Z-
dc.date.issued2013-06-18-
dc.identifier.citationBMC Nephrology. 2013 Jun 18;14(1):126-
dc.identifier.urihttp://dx.doi.org/10.1186/1471-2369-14-126-
dc.identifier.urihttp://hdl.handle.net/10147/295223-
dc.description.abstractAbstract Background 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. Methods 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. Results 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 < 0.05) associated with DN, however these SNPs did not remain significant after correction for multiple testing. Logistic regression of haplotypes, with ESRD as the outcome, and pairwise interaction analyses did not yield any significant results after correction for multiple testing. Conclusions These results indicate that both common SNPs and common haplotypes of WNT pathway genes are not strongly associated with DN. However, this does not completely exclude these or the WNT pathways from association with DN, as unidentified rare genetic or copy number variants could still contribute towards the genetic architecture of DN.-
dc.titleHaplotype association analysis of genes within the WNT signalling pathways in diabetic nephropathy-
dc.typeJournal Article-
dc.language.rfc3066en-
dc.rights.holderDavid H Kavanagh et al.; licensee BioMed Central Ltd.-
dc.description.statusPeer Reviewed-
dc.date.updated2013-07-04T11:09:36Z-
All Items in Lenus, The Irish Health Repository are protected by copyright, with all rights reserved, unless otherwise indicated.