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.
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.
Authors: Jussi Naukkarinen; Ida Surakka; Kirsi H Pietiläinen; Aila Rissanen; Veikko Salomaa; Samuli Ripatti; Hannele Yki-Järvinen; Cornelia M van Duijn; H-Erich Wichmann; Jaakko Kaprio; Marja-Riitta Taskinen; Leena Peltonen Journal: PLoS Genet Date: 2010-06-03 Impact factor: 5.917
Authors: Iris M Heid; Cornelia Huth; Ruth J F Loos; Florian Kronenberg; Vera Adamkova; Sonia S Anand; Kristin Ardlie; Heike Biebermann; Peter Bjerregaard; Heiner Boeing; Claude Bouchard; Marina Ciullo; Jackie A Cooper; Dolores Corella; Christian Dina; James C Engert; Eva Fisher; Francesc Francès; Philippe Froguel; Johannes Hebebrand; Robert A Hegele; Anke Hinney; Margret R Hoehe; Frank B Hu; Jaroslav A Hubacek; Steve E Humphries; Steven C Hunt; Thomas Illig; Marjo-Riita Järvelin; Marika Kaakinen; Barbara Kollerits; Heiko Krude; Jitender Kumar; Leslie A Lange; Birgit Langer; Shengxu Li; Andreas Luchner; Helen N Lyon; David Meyre; Karen L Mohlke; Vincent Mooser; Almut Nebel; Thuy Trang Nguyen; Bernhard Paulweber; Louis Perusse; Lu Qi; Tuomo Rankinen; Dieter Rosskopf; Stefan Schreiber; Shantanu Sengupta; Rossella Sorice; Anita Suk; Gudmar Thorleifsson; Unnur Thorsteinsdottir; Henry Völzke; Karani S Vimaleswaran; Nicholas J Wareham; Dawn Waterworth; Salim Yusuf; Cecilia Lindgren; Mark I McCarthy; Christoph Lange; Joel N Hirschhorn; Nan Laird; H-Erich Wichmann Journal: PLoS Genet Date: 2009-10-23 Impact factor: 5.917