Genome-Wide Association Scan Shows Genetic Variants in the FTO Gene Are Associated with Obesity-Related Traits

作者：Angelo Scuteri, Serena Sanna, Wei‐Min Chen, Manuela Uda, Giuseppe Albai, James Strait, Samer S. Najjar, Ramaiah Nagaraja, Marco Orrù, Gianluca Usala, Mariano Dei, Sandra Lai, Andrea Maschio, Fabio Busonero, Antonella Mulas, Georg Ehret, Ashley A Fink, Alan B. Weder, Richard S Cooper, Pilar Galán, Aravinda Chakravarti, David Schlessinger, Antonio Cao, Edward G. Lakatta, Gonçalo R. Abecasis · 发表于：PLoS Genetics · 年份：2007 · DOI：10.1371/journal.pgen.0030115 · 被引用次数：1738 · 研究领域：Genetic Associations and Epidemiology、Nutrition, Genetics, and Disease、Obesity, Physical Activity, Diet

The obesity epidemic is responsible for a substantial economic burden in developed countries and is a major risk factor for type 2 diabetes and cardiovascular disease. The disease is the result not only of several environmental risk factors, but also of genetic predisposition. To take advantage of recent advances in gene-mapping technology, we executed a genome-wide association scan to identify genetic variants associated with obesity-related quantitative traits in the genetically isolated population of Sardinia. Initial analysis suggested that several SNPs in the FTO and PFKP genes were associated with increased BMI, hip circumference, and weight. Within the FTO gene, rs9930506 showed the strongest association with BMI (p = 8.6 x10(-7)), hip circumference (p = 3.4 x 10(-8)), and weight (p = 9.1 x 10(-7)). In Sardinia, homozygotes for the rare "G" allele of this SNP (minor allele frequency = 0.46) were 1.3 BMI units heavier than homozygotes for the common "A" allele. Within the PFKP gene, rs6602024 showed very strong association with BMI (p = 4.9 x 10(-6)). Homozygotes for the rare "A" allele of this SNP (minor allele frequency = 0.12) were 1.8 BMI units heavier than homozygotes for the common "G" allele. To replicate our findings, we genotyped these two SNPs in the GenNet study. In European Americans (N = 1,496) and in Hispanic Americans (N = 839), we replicated significant association between rs9930506 in the FTO gene and BMI (p-value for meta-analysis of European American ...