A genome-wide scan for human obesity genes reveals a major susceptibility locus on chromosome 10

Nat Genet. 1998 Nov;20(3):304-8. doi: 10.1038/3123.


Obesity, a common multifactorial disorder, is a major risk factor for type 2 diabetes, hypertension and coronary heart disease (CHD). According to the definition of the World Health Organization (WHO), approximately 6-10% of the population in Westernized countries are considered obese. Epidemiological studies have shown that 30-70% of the variation in body weight may be attributable to genetic factors. To date, two genome-wide scans using different obesity-related quantitative traits have provided candidate regions for obesity. We have undertaken a genome-wide scan in affected sibpairs to identify chromosomal regions linked to obesity in a collection of French families. Model-free multipoint linkage analyses revealed evidence for linkage to a region on chromosome 10p (MLS=4.85). Two further loci on chromosomes 5cen-q and 2p showed suggestive evidence for linkage of serum leptin levels in a genome-wide context. The peak on chromosome 2 coincided with the region containing the gene (POMC) encoding pro-opiomelanocortin, a locus previously linked to leptin levels and fat mass in a Mexican-American population and shown to be mutated in obese humans. Our results suggest that there is a major gene on chromosome 10p implicated in the development of human obesity, and the existence of two further loci influencing leptin levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Chromosome Mapping
  • Chromosomes, Human, Pair 10 / genetics*
  • Female
  • Gene Frequency
  • Genetic Linkage
  • Genetic Markers
  • Genome, Human
  • Genotype
  • Humans
  • Leptin
  • Male
  • Obesity / blood
  • Obesity / genetics*
  • Phenotype
  • Proteins / genetics
  • Proteins / metabolism
  • Quantitative Trait, Heritable


  • Genetic Markers
  • Leptin
  • Proteins