# Presentation: 170598

## The Challenge – Maximizing the value of four different genetic studies of diabetes or diabetic complications

- FIND - Family Investigation of Nephropathy and Diabetes
- GoKinD - Genetics of Kidneys in Diabetes
- EDIC - Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications Study (EDIC)
- Type 1 Diabetes Genetics Consortium

## The Family Investigation of Nephropathy and Diabetes (FIND) StudyObjectives

- To utilize state-of-the-art genetic technology to identify genes for Diabetic Nephropathy
- A linkage study using diabetic relative pairs concordant or discordant for diabetic nephropathy.  All probands have biopsy-proved nephropathy and/or overt proteinuria (or ESRD)
- MALD, which uses markers with different allele frequency distributions in two founding populations of an admixed population as a tool for genome-wide mapping of susceptibility loci for both diabetic and non-diabetic kidney disease.

## Number of Participants

**Number of Participants**

|  | Families | Individuals |
| --- | --- | --- |
| African American | 399 | 1169 |
| American Indian | 264 | 1144 |
| European American | 222 | 706 |
| Mexican American | 561 | 2258 |
| Other Hispanic American | 11 | 29 |
| Other  | 5 | 18 |
| Total Recruited | 1462 | 5314 |

**MALD study – **recruitment to end in fall 2006
- Mexican-Americans - 841 cases, 452 hypernormal controls
- African-Americans - 278 diabetic nephropathy diads and triads, 478 non-diabetics diads and triads, 77 hypernormal controls

**Family study – **recruitment completed

## 	OVERALL GOALSThe overall goal of the GoKinD (“Genetics of Kidneys in Diabetes”) study is to establish a repository of DNA and clinical information from a large number of unrelated patients with type 1 diabetes in order to facilitate studies into the genetic basis of diabetic nephropathy.All probands (and cases) have overt proteinuria or ESRD.                                                       

##                   Enrollment (July, 2005)	   		  	TOTALCase Trio Probands:	  	    		271/600 Case Singletons:		  	  	674/500Total Cases: 			  	945/1100     Control Trio Probands: 	 	324/500Control Singletons:	 			620/500Total Controls: 			 	944/1000Total Probands:               	  	1889/2100

**           ****DNA and associated data are now available by application for all subjects ****See www.gokind.org****	****	****	****	****	****	****	****	****                                                                    **

## The DCCT demonstrated the efficacy of glycemic control for slowing the onset and progression of eye, kidney, and nerve diabetic complications.
In 1994, 96% of the participants were enrolled in EDIC for regular observational follow-up of metabolic and complications status, using similar methods as in the DCCT.
The goal of the EDIC Genetics substudy is to collect DNA, cells, serum and plasma on all available parents and at least one non-diabetic sib and measure diabetic complications on diabetic siblings

- In 1994, 96% of the participants were enrolled in EDIC for regular observational follow-up of metabolic and complications status, using similar methods as in the DCCT.
- The goal of the EDIC Genetics substudy is to collect DNA, cells, serum and plasma on all available parents and at least one non-diabetic sib and measure diabetic complications on diabetic siblings

- Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications Study (EDIC)

## Current collection (as of 2005)

- 1,419 DCCT/EDIC probands
- 2,960 relatives of DCCT/EDIC probands
- 806 mothers
- 582 fathers
- 1,572 siblings
- Of which 140 have diabetes and complications measured
- 4,379 individuals in total

## Type 1 Diabetes Genetics Consortium 

- 	**The goal of the Type 1 Diabetes Genetics Consortium is to organize international efforts to identify genes that determine an individual’s risk of type 1 diabetes, and to establish a renewable source of DNA on 2500 families with at least two type 1 diabetic children, one non-diabetic child and two parents. **

## Enrollment

**ASPs****	****	****	****	****1541**
**Minority Trios****	****	****41**

**DNA and data soon available **
**see www.t1dgc.org**

## RFA-DK-06-005  

- High-Density Genotyping of Diabetes and Diabetic Complications Sample Collections

-  Will support high-density genotyping of the EDIC and GoKIND collections.
- Genotyping data will be stored in an NIDDK repository and shared with the research community one year after it is generated.
- The participating Institutes (NIDDK, NHLBI, NIAID) will award up to $3.0 million for the first year and $2M for each of 2 additional years.
- Genotyping costs are NOT included.  Genotyping will be funded separately through direct NIDDK contracts
- Applications have already been received.
- Next year, a similar RFA will support genotyping of all 4 studies

## Challenges in receiving and repositing data 

- Need expertise in acquiring massive amounts of SNP genotype data
- Need system to link SNP data to associated genomic data
- Need way to link seamlessly to phenotypic databases that are complex and often have many versions
- Need to actively maintain phenotypic databases to assist investigators unfamiliar with the datasets
- Need to facilitate cross-study comparisons

## The NIDDK Central Database Repository will house the phenotypic data to be shared

- The NIDDK Central Database Repository will house the phenotypic data to be shared

## Challenges with data heterogeneity 

## Summary 

- Even when projects are studying the same phenotype, it may be difficult to compare subjects from different studies
- The requirements for storing SNP data are different from those for storing phenotypic data
- The complexity of phenotypic data may be a barrier for phenotype non-specialists