Independent confirmation of a major locus for obesity on chromosome 10

J Clin Endocrinol Metab. 2000 Aug;85(8):2962-5. doi: 10.1210/jcem.85.8.6852.

Abstract

Linkage results obtained in genome-wide scans for complex phenotypes require confirmation in independent samples. Recently, linkage of obesity to chromosome 10p12 with a maximal multipoint LOD score of 4.85 was reported upon use of an affected sib-pair approach including nuclear families in which the adult index case had a BMI > or = 40 kg/m2 and at least one further sibling had a BMI > or = 27 kg/m2 (Hager et al., 1998, Nat Genet 20:304-8). To attempt to replicate this linkage finding we genotyped 11 markers spanning approximately 23 cM from 10p13 to 10ql1 in a total of 386 individuals stemming from 93 nuclear families with two or more young obese offspring with a BMI > or = 90th age percentile. The highest multipoint maximum likelihood binomial (MLB) LOD score using the extreme concordant sib-pair approach in which one sib had a BMI > or = 95th percentile, and other sibs a BMI > or = 90th percentile was 2.32. Six markers yielded nominal p-values < 0.05, the highest two point MLB-LOD score of 2.45 (nominal p = 0.0004) was obtained for the marker TCF8. Transmission disequilibrium tests for the most frequent parental allele yielded no nominal p-value < 0.05. The linkage results confirm the presence of a major susceptibility locus for obesity in a region near the centromere on chromosome 10.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Body Mass Index
  • Chromosome Mapping
  • Chromosomes, Human, Pair 10*
  • Female
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Likelihood Functions
  • Lod Score
  • Male
  • Molecular Sequence Data
  • Nuclear Family
  • Obesity / genetics*

Substances

  • Genetic Markers

Associated data

  • GENBANK/M81699
  • GENBANK/U12170
  • GENBANK/Z51732