A genome-wide search for genes involved in type 2 diabetes in a recently genetically isolated population from the Netherlands

Diabetes. 2003 Dec;52(12):3001-4. doi: 10.2337/diabetes.52.12.3001.


Multiple genes, interacting with the environment, contribute to the susceptibility to type 2 diabetes. We performed a genome-wide search to localize type 2 diabetes susceptibility genes in a recently genetically isolated population in the Netherlands. We identified 79 nuclear families with type 2 diabetes who were related within 13 generations and performed a 770-marker genome-wide scan search for shared founder alleles. Twenty-six markers yielded a logarithm of odds (LOD) score >0.59 (nominal P < 0.05), of which 7 reached LOD scores >1.17 (nominal P < 0.01). The strongest evidence for a type 2 diabetes locus was at marker D18S63 on chromosome 18p (LOD 2.3, P = 0.0006). This region was investigated further using additional markers. For one of these markers (D18S1105), we found a significant association with type 2 diabetes (odds ratio 6.7 [95% CI 1.5-30.7], P = 0.005 for the 97-bp allele, assuming a dominant model), which increased when limiting the analysis to patients with high BMI (12.25 [2.1-71], P = 0.003). A locus on chromosome 18p in patients with high BMI was suggested earlier by Parker et al. Our study is the first to confirm this locus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Body Mass Index
  • Chromosome Mapping
  • Chromosomes, Human, Pair 18 / genetics
  • Demography
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / pathology
  • Founder Effect
  • Genes, Dominant
  • Genetic Markers
  • Genetic Predisposition to Disease / genetics
  • Genetic Testing*
  • Genome, Human*
  • Humans
  • Lod Score
  • Middle Aged
  • Netherlands


  • Genetic Markers