Original Paper

Familiality of Quantitative Metabolic Traits in Finnish Families with Non-Insulin-Dependent Diabetes mellitus
Richard M. Watanabe^a, Timo Valle^b, Elizabeth R. Hauser^a, Soumitra Ghosh^d, Johan Eriksson^b, Kimmo Kohtamäki^b, Christian Ehnholm^c, Jaakko Tuomilehto^b, Francis S. Collins^d, Richard N. Bergman^e, Michael Boehnke^a, for the Finland-United States Investigation of NIDDM Genetics (FUSION) Study Investigators

^aUniversity of Michigan, School of Public Health, Department of Biostatistics, Ann Arbor, Mich., USA,
^bNational Public Health Institute, Department of Epidemiology and Health Promotion, Diabetes and Genetic Epidemiology Unit, Helsinki, Finland,
^cNational Public Health Institute, Department of Biochemistry, Helsinki, Finland,
^dGenetics and Molecular Biology Branch, Laboratory of Gene Transfer, National Human Genome Research Institute, Bethesda, Md., USA,
^eUniversity of Southern California, School of Medicine, Department of Physiology & Biophysics, Los Angeles, Calif., USA

Address of Corresponding Author

Hum Hered 1999;49:159-168 (DOI: 10.1159/000022865)

  Key Words

• Heritability
• Variance components
• Pedigree analysis
• Genetics
• Glucose tolerance

  Abstract

Type 2 diabetes mellitus (NIDDM) is a complex disorder encompassing multiple metabolic defects. There exists strong evidence for a genetic component to NIDDM; however, to date there have been few reports of linkage between genetic markers along the genome and NIDDM or NIDDM-related quantitative traits. We sought to determine whether individual quantitative traits which determine glucose tolerance exhibit familiality in Finnish families with at least one NIDDM-affected sibling pair. Tolbutamide-modified frequently sampled intravenous glucose tolerance tests (FSIGT) were performed on unaffected offspring (n = 431) and spouses (n = 154) of affected sibling pairs sampled for the Finland-United States Investigation of NIDDM Genetics (FUSION) study. FSIGT data were analyzed using the Minimal Model to obtain quantitative measures of insulin sensitivity (S_I), glucose effectiveness (S_G), and insulin secretion assessed as the acute insulin response to glucose (AIR). The disposition index (DI), a measure of insulin resistance-corrected -cell function, was also derived as the product of S_I and AIR. Variance components analysis was used to determine for each trait, the heritability (h²), the proportion of the total trait variance accounted for by additive genes. After adjustment for age, gender, and body mass index, h² estimates were: S_G: 18 ± 9%, S_I: 28 ± 8%, AIR: 35 ± 8%, and DI: 23 ± 8%. We conclude that there is strong evidence for modest heritability of Minimal-Model-derived NIDDM-related quantitative traits in unaffected spouses and offspring of Finnish affected sibling pairs.

  Author Contacts

Dr. Richard M. Watanabe
University of Michigan, School of Public Health
Department of Biostatistics, 1420 Washington Heights
Ann Arbor, MI 48109-2029 (USA)
Tel. +1 734 647 3944, Fax +1 734 763 2215, E-Mail rwatt@sph.umich.edu

  Article Information

Received: Received: October 1, 1998
Accepted: October 16, 1998
Number of Print Pages : 10
Number of Figures : 0, Number of Tables : 7, Number of References : 41