Family Investigation of Nephropathy and Diabetes (FIND)

General Description

The Family Investigation of Nephropathy and Diabetes (FIND) was a multicenter observational study designed to identify genetic genetic determinants of diabetic kidney disease. Study participants were recruited from 11 centers and in many ethnic groups throughout the United States for a genome-wide association study (GWAS). Two additional strategies were also used to localize susceptibility genes: a family-based linkage study and a case-control study using mapping by admixture linkage disequilibrium (MALD). In the family-based study, participants with diabetic nephropathy were recruited with their parents and selected siblings. Linkage analyses were conducted to identify chromosomal regions containing genes that influence the development of diabetic nephropathy and related quantitative traits. Subsequently, a GWAS was carried out.

Two types of MALD studies were done. The first was a case-control study of unrelated individuals of Mexican American heritage in which both cases and controls had diabetes, but only the case had nephropathy. The second was a case-control study of African American patients with nephropathy (cases) and their spouses (controls) unaffected by diabetes and nephropathy; offspring were genotyped when available to provide haplotype data. Through the family and MALD studies, the FIND study identified several genes that contribute to diabetic nephropathy, albuminuria, and glomerular filtration rate (GFR), including ApoL1.

Note: Native American participants have been excluded due to consent to not share data.

Objectives

The primary aim of the FIND study was to identify genes responsible for diabetic nephropathy and their linkage relationships, if any, to nephropathy. Using environmental data as a guide for determining possible risk factor effects on genetic susceptibility was a secondary goal.

Outcome Measure

Quantitative measures such as glomerular filtration rate (GFR), the urine albumin:creatine ratio (ACR) and conditions including diabetic nephropathy and end-stage renal disease (ESRD) were used as traits in genome scans.

Criteria

Family Study:

The study enrolled individuals who had diabetes and diabetic nephropathy of 18 years of age or older. Participants were required to have both parents (regardless of the presence or absence of diabetes or nephropathy) or at least one full diabetic sibling with or without diabetic nephropathy available as potential study participants. Specific criteria for diabetic nephropathy are defined in detail in the protocol.

MALD Study:

In contrast to the family-based design, the MALD study used a case-control approach and enrolled only African-Americans or Mexican-Americans.

African-Americans: The study enrolled patients with nephropathy (cases) and their spouses (controls) unaffected by diabetes and nephropathy and their offspring (regardless of affection status).

Mexican-Americans: The study enrolled diabetic patients with (case) or without (control) nephropathy or ESRD attributed to diabetes.

Outcome

The FIND study identified several genes associated with diabetic nephropathy, albuminuria, and GFR through various analyses in the associated family and MALD studies, including ApoL1. The GWAS dataset is available via dbGAP.