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

Abstract

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.

A genome-wide scan for quantitative trait loci linked to obesity phenotypes among West Africans

“…This study provides substantial evidence for linkage supporting QTLs previously reported to be linked to serum leptin and plasma adiponectin levels. The linkage region on chromosome 2 in this study (with the peak at 72.6 cM for PBF) overlaps with the region found to be linked to leptin in several studies [14][15][16] and with the region linked to plasma adiponectin by Comuzzie et al 17 The linkage regions identified on chromosome 4 and 5 have not previously been reported as harboring QTLs influencing obesity phenotypes. Yet, the relatively strong linkage signals observed in this study suggest that these genomic regions may indeed contain QTLs influencing obesity traits.…”

Sex-specific findings from a genome-wide linkage analysis of human fatness in non-Hispanic whites and African Americans: The HyperGEN Study

“…Early reports indicated relatively consistent findings for 10p from three studies of US European American, French, and German cohorts. [19][20][21]63 Subsequently, several other reports on obesity-related phenotypes have found signals in the same or nearby chromosomal regions, but also including signals on 1q, 12 12,27 None of these studies have reported sex-specific linkage findings.…”

Proopiomelanocortin gene variants are associated with serum leptin and body fat in a normal female population

“…5 The POMC gene maps to chromosome 2p23.3. 6 A major quantitative trait locus (QTL) determining leptin levels has been linked to the POMC region in Mexican American families 7 and replicated in two other studies, 8,9 suggesting that variation in body mass index (BMI) or fat mass in the population might be linked to functional variant(s) in POMC coding or regulatory sequences.…”