Variance-component analysis of obesity in type 2 diabetes confirms loci on chromosomes 1q and 11q.
To study genetic loci influencing obesity in nuclear families with type 2 diabetes, we performed a genome-wide screen with 325 microsatellite markers that had an average spacing of 11 cM and a mean heterozygosity of approximately 75% covering all 22 autosomes. Genotype data were obtained from 562 individuals from 178 families from the Breda Study Cohort. These families were determined to have at least two members with type 2 diabetes. As a measure of obesity, the BMI of each diabetes patient was determined. The genotypes were analyzed using variance components (VCs) analysis implemented in GENEHUNTER 2 to determine quantitative trait loci influencing BMI. The VC analysis revealed two genomic regions showing VC logarithm of odds (LOD) scores > or =1.0 on chromosome 1 and chromosome 11. The regions of interest on both chromosomes were further investigated by fine-mapping with additional markers, resulting in a VC LOD score of 1.5 on chromosome 1q and a VC LOD of 2.4 on chromosome 11q. The locus on chromosome 1 has been implicated previously in diabetes. The locus on chromosome 11 has been implicated previously in diabetes and obesity. Our study to determine linkage for BMI confirms the presence of quantitative trait loci influencing obesity in subjects with type 2 diabetes on chromosomes 1q31-q42 and 11q14-q24.
van Tilburg
Jonathan H O
JH
Department of Biomedical Genetics, University Medical Center Utrecht, Stratenum 2.117, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands. t.n.wijmenga@med.uu.nl
Sandkuijl
Lodewijk A
LA
Strengman
Eric
E
Pearson
Peter L
PL
van Haeften
Timon W
TW
Wijmenga
Cisca
C
D000368:Aged; D000704:Analysis of Variance; D015992:Body Mass Index; D002878:Chromosomes, Human, Pair 1; D002880:Chromosomes, Human, Pair 11; D003920:Diabetes Mellitus / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009765:Obesity; D040641:Quantitative Trait Loci