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

Study Overview
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Brief Summary
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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....

Detailed Description
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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.

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

Conditions
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Genetic Variation, Diabetes

Participation Criteria
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Eligibility Criteria
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No eligibility criteria listed.

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Monogenic Diabetes, Type 2 Diabetes Mellitus, QTL