A genome-wide scan for human obesity genes reveals a major susceptibility locus on chromosome 10.
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.
Hager
J
J
Institut de Biologie de Lille, CNRS EP10, France.
Dina
C
C
Francke
S
S
Dubois
S
S
Houari
M
M
Vatin
V
V
Vaillant
E
E
Lorentz
N
N
Basdevant
A
A
Clement
K
K
Guy-Grand
B
B
Froguel
P
P
D000483:Alleles; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D005819:Genetic Markers; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D020738:Leptin; D008297:Male; D009765:Obesity / Q000097:blood / Q000235:genetics*; D010641:Phenotype; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D019655:Quantitative Trait, Heritable
D005819:Genetic Markers; D020738:Leptin; D011506:Proteins