Search for Susceptibility Genes for Diabetic Nephropathy in Type 1 Diabetes (GoKinD study participants), GAIN

Genetics of Kidneys in Diabetes (GoKinD) study is an initiative aimed at identifying susceptibility genes for diabetic nephropathy in type 1 diabetes. A large number of individuals with type 1 diabetes were screened to identify two subsets, one with clear-cut kidney disease and another with normal renal status despite long-term diabetes. Those who met additional entry criteria and consented to participate were enrolled. When possible, both parents were also enrolled to form family trios. Altogether, GoKinD includes 3043 participants comprising 931 cases, 944 singletons, 268 pairs of parents of cases, and 316 pairs of parents of control. Accessible as a GAIN database are 905 of the cases, 890 of the controls, 10 pairs of parents of cases and 10 pairs of parents of controls. The other parents and the remaining cases and controls are available by a separate application process through NIDDK (dbGaP phs000088 Search for Susceptibility Genes for Diabetic Nephropathy in Type 1 Diabetes (GoKinD study participants and parents), NIDDK). Interested investigators may request the DNA collection and corresponding clinical data for GoKinD participants using the instructions and application form available at Juvenile Diabetes Research Foundation. Consent groups and participant set Diabetic complications only (DCO): 1825 (904 cases, 881 controls, 40 others) ]]>
GoKinD GW Clinics Derived variables SAS code documentationGoKinD Joslin Derived variables SAS code documentationPersonal Information on Proband/RelativeNotification of DeathNotification of Transfer, Remote Site Collection, or Refusal to ParticipateMedical History and Physical ExaminationCurrent Medication FormHistorical Urine Value for Control ProbandsChecklist for Proband/RelativesHOW TO GET STARTED AS A NEW SITE, 1RECRUITMENT AND SCREENING PROCEDURE, 2GUIDELINES FOR OBTAINING INFORMED CONSENT, 3SCREENING BASELINE VISIT, 4QUALITY CONTROL AND INTERNAL MONITORING, 5GOKIND FORMS COMPLETION AND MAILING OF FORMS, 6REIMBURSEMENT, 7LABORATORY SPECIMENS AND THE CENTRAL BIOCHEMISTRY LABORATORY, 8GOKIND DATA AND INFORMATION TRANSFER, 10GoKinD Study Diabetic OffspringGoKinD Study ParentsProtocolGenotyping of the DQA1 gene in the HLA ComplexGenotyping of the HLA-DQB1 GeneSequence-Based Typing of the HLA-DRB 1 geneDetection of the Insulin Gene Hph I Polymorphism using Sequence Specific Oligonucleotides (SSO)CDC Methods for Genotype Determination for the Following Genes:Authorized access to GAIN Project Datasets: Application Instructions (retired document)Authorized access to GAIN Project Datasets: Application Instructionspre-computed by NCBI using the Affy 5.0 platform. SNPs were selected for analysis of minor allele frequencies ≥ 0.03, call rate ≥ 95%, Hardy-Weinberg p-values ≥ 0.000001, producing a total set of 364292 SNPs analyzed.
]]>-5 ) and minor allele frequency (MAF) > 1%, as well as genotyping completeness (3-stage filter: < 95% for SNPs with MAF 10% or higher , < 97% for SNPs with MAF between 5% and 10%, < 99% for SNPs with MAF between 1% and 5%). This resulted in the inclusion of 359,193 of the 467,144 autosomal SNPs in the Affymetrix data provided by the GAIN laboratory. Analysis of cryptic relationships (using GRR and PREST), duplication, sample genotyping quality, and population ancestry (using EIGENSOFT), reduced the samples for analysis to 1,705 samples of European ancestry (including 820 diabetic nephropathy cases and 885 normoalbuminuric controls).
]]>pre-computed by NCBI. Of these trios, 223 are affected and 263 are unaffected. The offspring samples were collected from the Genetics of Kidneys in Diabetes (GoKinD) study (dbGaP phs000018, "Search for Susceptibility Genes for Diabetic Nephropathy in Type 1 Diabetes [GoKinD study participants and parents]"). Parents were enrolled with unknown affection status to form trios. All samples were genotyped by the Genetic Association Information Network (GAIN) genotyping laboratory at the Eli and Edythe L. Broad Institute on the Affymetrix 5.0 500K SNP Array. SNP markers were filtered for parent Hardy-Weinberg disequilibrium (P < 10-4 ), or minor allele frequency (MAF < 1%), or call rate (< 95%), as well as ones with more than 5 Mendelian errors. This resulted in the inclusion of 358298 SNPs. Six unaffected trios were excluded owing to the high familial Mendelian errors (>1%).
]]>Inclusion criteria Probands for this data collection must have type 1 diabetes and either presence or absence of diabetic nephropathy according to the following definitions: Type 1 diabetes is diagnosed if: Subject had diabetes diagnosed before age 31 Treatment with insulin was instituted within one year of diagnosis Treatment with insulin has been uninterrupted since diagnosis Presence of diabetic nephropathy is diagnosed if: Subject with diabetes for at least 10 years has persistent proteinuria or ESRD (not due to condition other than diabetes). Persistent proteinuria is defined as at least 2 of 3 tests positive for albuminuria (at least 1 month apart), i.e., dipstick (Albustix or Multistix) at least 1+ or ACR value exceeding 300 μg albumin/mg of urine creatinine. Absence of diabetic nephropathy is diagnosed if: Subject has persistent normoalbuminuria despite duration of type 1 diabetes for at least 15 years and has never been treated with ACE inhibitors. Persistent normoalbuminuria is defined as at least 2 of 3 ACR measurements (at least 1 month apart) in random urine specimen being less than 20 μg of albumin/mg of creatinine. If 3 ACR measurements are needed, the highest must also be less than 40 μg of albumin/mg of creatinine. Exclusion criteria Individuals will be excluded from the study if they do not meet the inclusion criteria described above or if any of the following exclusion criteria are met: Unable or unwilling to give informed consent Unable to communicate with staff Major psychiatric disorder such as schizophrenia Exclusion in relation to medication Any antihypertensive medication for controls Infectious disease Self-reported HIV positivity Active tuberculosis Other kidney disease in cases Alport syndrome Analgesic nephropathy Atheroembolic renal disease Congenital nephrotic syndrome Focal segmental glomerulosclerosis (FSGS) Glomerulonephritis Goodpasture's syndrome HIV nephropathy IgM mesangial proliferative nephritis Lupus nephritis Kidney cancer IgA nephropathy Polycystic kidney disease Urinary tract infection (Note: infectious processes such as cystitis and urinary tract infections do not represent a permanent exclusion. Patients may be recontacted or asked to send a supplemental urine sample at a later date.) Pregnant women (although they may be reconsidered 3 months after delivery)]]>