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.
Aulchenko
Yurii S
YS
Department of Epidemiology & Biostatistics, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands.
Vaessen
Norbert
N
Heutink
Peter
P
Pullen
Jan
J
Snijders
Pieter J L M
PJ
Hofman
Albert
A
Sandkuijl
Lodewijk A
LA
Houwing-Duistermaat
Jeanine J
JJ
Edwards
Mark
M
Bennett
Simon
S
Oostra
Ben A
BA
van Duijn
Cornelia M
CM
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
D005819:Genetic Markers