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

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Abstract

Obesity, 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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Figure 1: Multipoint analyses results with the most significant evidence for linkage on chromosomes 10, 2 and 5.
Figure 2: Multipoint analyses results for all chromosomes.

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Acknowledgements

We thank the patients for their participation to this study. We also thank the Assistance Publique/Hôpitaux de Paris (AP/HP) and the Programme Hôspitalier de Recherche Clinique (PHRC) for their support. We are grateful for the constructive discussions and help with the statistical analyses by M. Lathrop and M. Farrall. J.H. and E.V. were supported through European grant program BIOMED2 BMH4-CT950662.

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Correspondence to Jörg Hager or Philippe Froguel.

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