A genome-wide search for genes involved in type 2 diabetes in a recently genetically isolated population from the Netherlands
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.
|Keywords||*Genetic Screening, *Genome, Human, 0 (Genetic Markers), Alleles, Body Mass Index, Chromosome Mapping, Chromosomes, Human, Pair 18/genetics, Demography, Diabetes Mellitus, Type II/*genetics/pathology, Diabetes and related disorders, Founder Effect, Genes, Dominant, Genetic Markers, Genetic Predisposition to Disease/genetics, Human, Lod Score, Middle Aged, Netherlands, Support, Non-U.S. Gov't|
|Persistent URL||dx.doi.org/10.2337/diabetes.52.12.3001, hdl.handle.net/1765/5939|
Aulchenko, Y.S., Vaessen, N., Heutink, P., Pullen, J., Snijders, P.J.L.M., Hofman, A., … Edwards, M.. (2003). A genome-wide search for genes involved in type 2 diabetes in a recently genetically isolated population from the Netherlands. Diabetes, 52(12), 3001–3004. doi:10.2337/diabetes.52.12.3001