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

J Hager, C Dina, S Francke, S Dubois, M Houari… - Nature …, 1998 - nature.com
J Hager, C Dina, S Francke, S Dubois, M Houari, V Vatin, E Vaillant, N Lorentz, A Basdevant…
Nature genetics, 1998nature.com
Obesity, a common multifactorial disorder, is a major risk factor for type 2 diabetes,
hypertension and coronary heart disease 1 (CHD). According to the definition of the World
Health Organization (WHO), approximately 6-10% of the population in Westernized
countries are considered obese 2. 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 …
Abstract
Obesity, a common multifactorial disorder, is a major risk factor for type 2 diabetes, hypertension and coronary heart disease 1 (CHD). According to the definition of the World Health Organization (WHO), approximately 6-10% of the population in Westernized countries are considered obese 2. 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 3, 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 population 3 and shown to be mutated in obese humans 5. 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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