A Quantitative Trait Locus Influencing Type 2 Diabetes Susceptibility Maps to a Region on 5q in an Extended French Family

  1. Lisa J. Martin12,
  2. Anthony G. Comuzzie2,
  3. Sophie Dupont3,
  4. Nathalie Vionnet4,
  5. Christian Dina3,
  6. Sophie Gallina3,
  7. Mouna Houari3,
  8. John Blangero2 and
  9. Philippe Froguel35
  1. 1Center for Epidemiology and Biostatistics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio
  2. 2Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas
  3. 3Institute of Biology, Institute Pasteur of Lille, Lille, France
  4. 4Centre National de Génotypage, Evry Cedex, France
  5. 5Barts & The London Genome Centre, Queen Mary & Smithfield College, London, U.K

    Abstract

    Type 2 diabetes is a heterogeneous disorder of glucose metabolism characterized by insulin resistance, β-cell dysfunction, and increased glucose production by the liver. Given the high degree of genetic heterogeneity, multiple genes with small to moderate effects may influence susceptibility to diabetes. To circumvent this limitation, we searched for quantitative trait loci (QTLs) that explain the variation in susceptibility of type 2 diabetes in a single extended family, as these individuals are likely to share polymorphisms. We collected genotypic and phenotypic data on 152 individuals ascertained through a multimedia campaign in France to find diabetes-prone families for genetic studies. The effects of genes and covariates (age and sex) on diabetes status were estimated using a threshold model and a maximum likelihood variance component approach. We obtained suggestive evidence of linkage (logarithm of odds [LOD] = 2.4) for diabetes status on chromosome 5q. Within the 1-LOD unit support interval, there are two strong candidates: PCSK1 and CAST. Furthermore, we have obtained a replication (LOD = 1.6) for a QTL for type 2 diabetes on chromosome 11 detected by Hanson and colleagues (1998).

    Footnotes

    • Address correspondence and reprint requests to Lisa Martin, Center for Epidemiology and Biostatistics, Cincinnati Children’s Hospital Medical Center, 2800 Winslow, Room 2110, Mail Code 5041, Cincinnati OH 45229. E-mail: lisa.martin{at}cchmc.org.

      Received for publication 18 April 2002 and accepted in revised form 16 September 2002.

      IBD, identity by descent; IGT, impaired glucose tolerance; LOD, logarithm of odds; QTL, quantitative trait locus.

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