title: A genome-wide search for genes involved in type 2 diabetes in a recently genetically isolated population from the Netherlands.
abstract: 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.
authors.affiliation: Department of Epidemiology & Biostatistics, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Yurii S
authors.initials: YS
authors.lastname: Aulchenko
authors.forename: Norbert
authors.initials: N
authors.lastname: Vaessen
authors.forename: Peter
authors.initials: P
authors.lastname: Heutink
authors.forename: Jan
authors.initials: J
authors.lastname: Pullen
authors.forename: Pieter J L M
authors.initials: PJ
authors.lastname: Snijders
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Lodewijk A
authors.initials: LA
authors.lastname: Sandkuijl
authors.forename: Jeanine J
authors.initials: JJ
authors.lastname: Houwing-Duistermaat
authors.forename: Mark
authors.initials: M
authors.lastname: Edwards
authors.forename: Simon
authors.initials: S
authors.lastname: Bennett
authors.forename: Ben A
authors.initials: BA
authors.lastname: Oostra
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
mesh_terms: D000483:Alleles; D015992:Body Mass Index; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D003710:Demography; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology; D018703:Founder Effect; D005799:Genes, Dominant; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D015894:Genome, Human; D006801:Humans; D008126:Lod Score; D008875:Middle Aged; D009426:Netherlands
chemical_list: D005819:Genetic Markers