Nature Genetics
20, 304 - 308 (1998)
doi:10.1038/3123
A genome-wide scan for human obesity genes reveals a major susceptibility
locus on chromosome 10Jörg Hager1, 3, Christian Dina1, Stephan Francke1, Severine Dubois1, Mouna Houari1, Vincent Vatin1, Emmanuel Vaillant1, Nathalie Lorentz1, Arnaud Basdevant2, Karine Clement1, 2, Bernard Guy-Grand2
& Philippe Froguel11
Institut de Biologie de Lille, CNRS EP10,
1 rue du Prof Calmette, 59019 Lille,
France. 2
Department of Nutrition, Hôtel Dieu Hospital, Paris, France. 3
Institut für klinische Biochemie, Universität Bonn, Bonn, Germany.
Correspondence should be addressed to Philippe Froguel froguel@xenope.pasteur-lille.fr or jorg.hager@xenope.pasteur-lille.frObesity, a common multifactorial disorder, is a major risk factor for type
2 diabetes, hypertension and coronary heart disease1 (CHD).
According to the definition of the World Health Organization (WHO), approximately
6-10% of the population in Westernized countries are considered obese2. 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 obesity3,
4. 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
population3 and shown to be mutated in obese humans5.
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.
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