Mapping Genes for Type 2 (Non-Insulin Dependent) Diabetes Mellitus

The aim of the project is to positionally clone susceptibility genes for NIDDM. Patients will be ascertained in Finland from previous health surveys and hospital discharge records. Approximately 400 affected sib pairs will be collected. Families will be chosen who have, at most, one parent with NIDDM no history of IDDM. A clinical examination will be undertaken on family members and blood drawn for DNA isolation. Covariates such as body weight, blood pressure, lipid levels and urinary albumin will also be measured. The unaffected spouse and children of a subset of probands will be invited to undergo a frequently-sampled intravenous glucose tolerance test (FSIGT) to measure parameters of pancreatic function and peripheral insulin resistance (IR). A number of unrelated elderly non-diabetic subjects will also be identified to conduct a population-based association analysis.

The FSIGT analysis will be performed in Los Angeles. The DNA will be shipped to Bethesda where a total genomic scan will be performed using semi-automated fluorescence-based genotyping technology. Data from Bethesda, Los Angeles and Finland will be sent to Ann Arbor where parametric and non-parametric methods will be used to analyse both discrete traits such as NIDDM and intermediate traits like IR....

Study Overview

• Status: Completed
• Conditions: Diabetes; Genetic Variation

Detailed Description

The Finland-United States investigation of NIDDM (FUSION) study is a long-term effort to

identify susceptibility genes for Type 2 diabetes (T2D) and associated quantitative traits. This

involves the phenotyping and DNA analysis of thousands of individuals living in Finland, utilizing a study design that was originally based on affected sib pairs. The majority of these samples have already been subjected to a genome scan using microsatellite markers and the original FUSION samples. Additionally, thousands of other northern European cases and controls have been subjected to genome-wide association (GWA) analysis and/or fine mapping as part of the FUSION study. More recently, the opportunity provided by the lowered sequencing costs have allowed targeted and/or whole genome sequencing of many of these individuals.

• Study Type: Observational
• Enrollment (Actual): 32379

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland
    • Natl Inst for Health & Welfare (THL)
  • Kuopio, Finland
    • Research Ethics Committee of Hospital District of Northern Savo
• Norway
  • Tromso, Norway
    • University of Tromso
  • Trondheim, Norway
    • Norwegian U of Science & Technology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

A large majority of the sample population resides in various parts of Finland and are of Finnish descent. The Finnish population provides an ideal basis for studies of complex genetic diseases such as T2D due to its relative genetic and environmental homogeneity, excellent data sources, and a population strongly supportive of biomedical research. Individuals with or without diabetes (type2 or monogenic forms of diabetes) have been collected.

Description

• No eligibility criteria listed.

Study Plan

How is the study designed?

Number of groups / cohorts

16

Cohorts and Interventions

Group / Cohort
AADM; Family and Population based individuals
Action-LADA; Population based individuals
D2D 2004; Population based individuals
DIAGEN (Dresden Biobank); Population based individuals
FINRISK 1987; Population based individuals
FINRISK 2002; Population based individuals; Test DNA
Fusion 1; Affected-sib pair (ASP) families and elderly controls
Fusion 2; 275 Replication ASP Families; Trios
Fusion 3; Siblings of FUSION1 families; Spouses, Offspring of 291 FUSION 1 families; Spouses, Offspring of Elderly Controls; Other F1 relatives
Fusion 4/5; Spouses, Offspring of FUSION 1 and 2 Families
FUSION Finnish Groups; Family and Population based (including METSIM and DR's EXTRA): Tissue samples
Health-2000; Population based individuals
HUNT 2; Population based individuals
METSIM; Population based individuals
Savitaipale; Population based individuals
UEF - Laakso; Monogenic disease individuals and family members

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
T2D status, quantitative traits measurements	Association testing	ongoing

Collaborators and Investigators

• Sponsor: National Human Genome Research Institute (NHGRI)
• Investigators: Principal Investigator: Lori Bonnycastle, Ph.D., National Human Genome Research Institute (NHGRI)

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 1996
• Primary Completion (Actual): May 22, 2020
• Study Completion (Actual): May 22, 2020

Study Registration Dates

• First Submitted: June 19, 2006
• First Submitted That Met QC Criteria: June 19, 2006
• First Posted (Estimate): June 21, 2006

Study Record Updates

• Last Update Posted (Actual): May 27, 2020
• Last Update Submitted That Met QC Criteria: May 22, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Type 2 Diabetes Mellitus; Monogenic Diabetes; QTL
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus
• Other Study ID Numbers: 999995030; OH95-HG-N030

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No