Dataset Information

Association testing of previously reported variants in a large case-control meta-analysis of diabetic nephropathy.

ABSTRACT: We formed the GEnetics of Nephropathy-an International Effort (GENIE) consortium to examine previously reported genetic associations with diabetic nephropathy (DN) in type 1 diabetes. GENIE consists of 6,366 similarly ascertained participants of European ancestry with type 1 diabetes, with and without DN, from the All Ireland-Warren 3-Genetics of Kidneys in Diabetes U.K. and Republic of Ireland (U.K.-R.O.I.) collection and the Finnish Diabetic Nephropathy Study (FinnDiane), combined with reanalyzed data from the Genetics of Kidneys in Diabetes U.S. Study (U.S. GoKinD). We found little evidence for the association of the EPO promoter polymorphism, rs161740, with the combined phenotype of proliferative retinopathy and end-stage renal disease in U.K.-R.O.I. (odds ratio [OR] 1.14, P = 0.19) or FinnDiane (OR 1.06, P = 0.60). However, a fixed-effects meta-analysis that included the previously reported cohorts retained a genome-wide significant association with that phenotype (OR 1.31, P = 2 × 10(-9)). An expanded investigation of the ELMO1 locus and genetic regions reported to be associated with DN in the U.S. GoKinD yielded only nominal statistical significance for these loci. Finally, top candidates identified in a recent meta-analysis failed to reach genome-wide significance. In conclusion, we were unable to replicate most of the previously reported genetic associations for DN, and significance for the EPO promoter association was attenuated.

SUBMITTER: Williams WW

PROVIDER: S-EPMC3402313 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association testing of previously reported variants in a large case-control meta-analysis of diabetic nephropathy.

Williams Winfred W WW Salem Rany M RM McKnight Amy Jayne AJ Sandholm Niina N Forsblom Carol C Taylor Andrew A Guiducci Candace C McAteer Jarred B JB McKay Gareth J GJ Isakova Tamara T Brennan Eoin P EP Sadlier Denise M DM Palmer Cameron C Söderlund Jenny J Fagerholm Emma E Harjutsalo Valma V Lithovius Raija R Gordin Daniel D Hietala Kustaa K Kytö Janne J Parkkonen Maija M Rosengård-Bärlund Milla M Thorn Lena L Syreeni Anna A Tolonen Nina N Saraheimo Markku M Wadén Johan J Pitkäniemi Janne J Sarti Cinzia C Tuomilehto Jaakko J Tryggvason Karl K Österholm Anne-May AM He Bing B Bain Steve S Martin Finian F Godson Catherine C Hirschhorn Joel N JN Maxwell Alexander P AP Groop Per-Henrik PH Florez Jose C JC

Diabetes 20120620 8

We formed the GEnetics of Nephropathy-an International Effort (GENIE) consortium to examine previously reported genetic associations with diabetic nephropathy (DN) in type 1 diabetes. GENIE consists of 6,366 similarly ascertained participants of European ancestry with type 1 diabetes, with and without DN, from the All Ireland-Warren 3-Genetics of Kidneys in Diabetes U.K. and Republic of Ireland (U.K.-R.O.I.) collection and the Finnish Diabetic Nephropathy Study (FinnDiane), combined with reanaly ...[more]

PMID: 22721967

Similar Datasets

Project description:BackgroundDiabetic nephropathy is the most serious complication of diabetes which leads to end-stage renal failure and other complication of diabetes mellitus. Determinants of Diabetic nephropathy are not consistent in different studies and associated factors to chronic complications of diabetes are not specific and there are limited studies specific to diabetic nephropathy. Thus, the aim of this study is to identify determinants of diabetic nephropathy in Ayder Referral Hospital, Northern Ethiopia.MethodsA case-control study was conducted from February 14 to May 8 2016. Diabetic patients who developed nephropathy in the last two years were the cases and diabetic patients free of nephropathy were controls. Cases and controls were identified detailed review of the chronic care follow up chart. Then simple random sampling was used to select sample of 420 (with control to case ratio of 4:1) resulting in 84 cases and 336 controls. Record review and interviewer administered questionnaire were used to collect data. Data was coded and entered in to Epi-Data version 3.1 and then exported to STATA 12 for analysis. Variables with P-values< 0.25 in Bivariate logistic regression were selected for multiple logistic regressions to determine independent determinants of diabetic nephropathy. OR was calculated with 95% CI to show strength of association.ResultThe mean age (±Standard deviation) for the cases and the controls were 52(SD: ±1.34) and 42.4(SD: ±0.8) respectively. In multiple logistic regressions age of patient (AOR: 1.037 95%CI: 1.01-1.064), duration of diabetes after diagnosis (AOR for one year increase: 1.09 95%CI: 1.036-1.15), not-adhered to blood glucose measurement at home (AOR: 6.81 95%CI: 1.15-40.24), having Systolic Hypertension (AOR;2.13 (1.002-4.51), poor glycemic control (AOR;2.71 95%CI: (1.49-4.95), being overweight(AOR;2.7(1.47-4.96) were the independent predictors of diabetic nephropathy.ConclusionIn the light of these findings, targeted interventions should be designed at the follow up clinic to address the risk of developing diabetic nephropathy among the risk groups.

Project description:BackgroundColorectal cancer (CRC) is the second leading cause of cancer death in developed countries. Familial aggregation in CRC is also important outside syndromic forms and, in this case, a polygenic model with several common low-penetrance alleles contributing to CRC genetic predisposition could be hypothesized. Mucins and GALNTs (N-acetylgalactosaminyltransferase) are interesting candidates for CRC genetic susceptibility and have not been previously evaluated. We present results for ten genetic variants linked to CRC risk in previous studies (previously identified category) and 18 selected variants from the mucin gene family in a case-control association study from the Spanish EPICOLON consortium.MethodsCRC cases and matched controls were from EPICOLON, a prospective, multicenter, nationwide Spanish initiative, comprised of two independent stages. Stage 1 corresponded to 515 CRC cases and 515 controls, whereas stage 2 consisted of 901 CRC cases and 909 controls. Also, an independent cohort of 549 CRC cases and 599 controls outside EPICOLON was available for additional replication. Genotyping was performed for ten previously identified SNPs in ADH1C, APC, CCDN1, IL6, IL8, IRS1, MTHFR, PPARG, VDR and ARL11, and 18 selected variants in the mucin gene family.ResultsNone of the 28 SNPs analyzed in our study was found to be associated with CRC risk. Although four SNPs were significant with a P-value < 0.05 in EPICOLON stage 1 [rs698 in ADH1C (OR = 1.63, 95% CI = 1.06-2.50, P-value = 0.02, recessive), rs1800795 in IL6 (OR = 1.62, 95% CI = 1.10-2.37, P-value = 0.01, recessive), rs3803185 in ARL11 (OR = 1.58, 95% CI = 1.17-2.15, P-value = 0.007, codominant), and rs2102302 in GALNTL2 (OR = 1.20, 95% CI = 1.00-1.44, P-value = 0.04, log-additive 0, 1, 2 alleles], only rs3803185 achieved statistical significance in EPICOLON stage 2 (OR = 1.34, 95% CI = 1.06-1.69, P-value = 0.01, recessive). In the joint analysis for both stages, results were only significant for rs3803185 (OR = 1.12, 95% CI = 1.00-1.25, P-value = 0.04, log-additive 0, 1, 2 alleles) and borderline significant for rs698 and rs2102302. The rs3803185 variant was not significantly associated with CRC risk in an external cohort (MCC-Spain), but it still showed some borderline significance in the pooled analysis of both cohorts (OR = 1.08, 95% CI = 0.98-1.18, P-value = 0.09, log-additive 0, 1, 2 alleles).ConclusionsARL11, ADH1C, GALNTL2 and IL6 genetic variants may have an effect on CRC risk. Further validation and meta-analyses should be undertaken in larger CRC studies.

Dataset Information

Association testing of previously reported variants in a large case-control meta-analysis of diabetic nephropathy.

Publications

Association testing of previously reported variants in a large case-control meta-analysis of diabetic nephropathy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets