Abstract

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 so far and relatively few regions have been replicated. 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 are sampled from Campora, an isolated village of the Cilento area in South Italy, phenotyped for body mass index (BMI) and genotyped a dense microsatellite marker map. An efficient pedigree-breaking strategy is applied to perform genome-wide linkage analyses of both BMI and obesity. Significance is assessed with ad hoc simulations for the two traits and with an original lFDR approach to quantitative trait linkage analysis for BMI. A genealogy-corrected association test is performed for a SNP located in one of the linkage regions. A replication study is conducted in the neighboring village of Gioi.

Results: A new locus on chr1q24 significantly linked to BMI is identified in Campora. Linkage at the same locus is suggested with obesity. Three additional loci linked to BMI are also detected. Among them, the locus including the INSIG2 gene region. No evidence of association between the rs7566605 variant and BMI or obesity is found. In Gioi, the linkage on chr1q24 is 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 QTLs.