Computational protocol: Confirmation of Genetic Associations at ELMO1 in the GoKinD Collection Supports Its Role as a Susceptibility Gene in Diabetic Nephropathy

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Protocol publication

[…] A detailed description of the Genetics of Kidneys in Diabetes (GoKinD) study collection has been published previously (). Briefly, subjects for the GoKinD collection were recruited through two centers: the George Washington University (GWU) Biostatistics Center and the Section of Genetics and Epidemiology at the Joslin Diabetes Center (JDC). Subjects enrolled in GoKinD by either recruitment center had type 1 diabetes diagnosed before age 31 years, began insulin treatment within 1 year of diagnosis, and were between 18 and 59 years of age at the time of enrollment. Case subjects with advanced diabetic nephropathy had either persistent proteinuria, defined by a urinary albumin-to-creatinine ratio (ACR) ≥300 μg/mg in two of the last three measurements taken at least 1 month apart, or ESRD (dialysis or renal transplant). Control subjects had type 1 diabetes for at least 15 years and normoalbuminuria, defined by an ACR <20 μg/mg in two of the last three measurements taken at least 1 month apart (if a third measurement was required, a value <40 μg/mg was necessary for inclusion), without ever having been treated with ACE inhibitors or angiotensin receptor blockers and not being treated with antihypertensive medication at the time of recruitment into the study. A total of 1,705 individuals (885 control subjects and 820 advanced diabetic nephropathy case subjects, including 284 with proteinuria and 536 with ESRD) of European ancestry (confirmed by population ancestry and substructure analysis using EIGENSOFT; for further details see Pezzolesi et al. []) were included in the current study (). [...] Linkage disequilibrium (LD) blocks were defined using the method of Gabriel et al. () as implemented in Haploview version 4.1 (). All SNPs were analyzed using stratified additive tests of association (adjusting for both sex and JDC/GWU strata) using the Cochran-Mantel-Haenzel test procedure to calculate combined P values and odds ratios (ORs). Associations with diabetic nephropathy were also assessed under both dominant and recessive genetic models. All statistical and haplotype analyses were performed using PLINK (). […]

Pipeline specifications

Software tools EIGENSOFT, Haploview, PLINK
Applications Population genetic analysis, GWAS
Diseases Diabetes Mellitus, Diabetic Nephropathies, Kidney Diseases