Identification and Replication of a Novel Obesity Locus on Chromosome 1q24 in Isolated Populations of Cilento

Ciullo, Marina; Nutile, Teresa; Dalmasso, Cyril; Sorice, Rossella; Bellenguez, Céline; Colonna, Vincenza; Persico, Maria Graziella; Bourgain, Catherine
March 2008
Diabetes;Mar2008, Vol. 57 Issue 3, p783
Academic Journal
OBJECTIVE--Obesity is a complex trait with a variety of genetic susceptibility variants. Several loci linked to obesity and/or obesity-related traits have been identified, and relatively few regions have been replicated. Studying isolated populations can be a useful approach to identify rare variants that will not be detected with whole-genome association studies in large populations. RESEARCH DESIGN AND METHODS--Random individuals were sampled from Campora, an isolated village of the Cilento area in South Italy, phenotyped for BMI, and genotyped using a dense microsatellite marker map. An efficient pedigree-breaking strategy was applied to perform genome-wide linkage analyses of both BMI and obesity. Significance was assessed with ad hoc simulations for the two traits and with an original local false discovery rate approach to quantitative trait linkage analysis for BMI. A genealogy-corrected association test was performed for a single nucleotide polymorphism located in one of the linkage regions. A replication study was conducted in the neighboring village of Gioi. RESULTS--A new locus on chr1q24 significantly linked to BMI was identified in Campora. Linkage at the same locus is suggested with obesity. Three additional loci linked to BMI were also detected, including the locus including the INSIG2 gene region. No evidence of association between the rs7566605 variant and BMI or obesity was found. In Gioi, the linkage on chr1q24 was replicated with both BMI and obesity. CONCLUSIONS--Overall, our results confirm that successful linkage studies can be accomplished in these populations both to replicate known linkages and to identify novel quantitative trait linkages. Diabetes 57:783-790, 2008


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