Genome wide association (GWA) study for early onset extreme obesity supports the role of fat mass and obesity associated gene (FTO) variants

Obesity is a major health problem. Although heritability is substantial, genetic mechanisms predisposing to obesity are not very well understood. We have performed a genome wide association study (GWA) for early onset (extreme) obesity. a) GWA (Genome-Wide Human SNP Array 5.0 comprising 440,794 sing...

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Published in:	PloS one 2007-12, Vol.2 (12), p.e1361-e1361
Main Authors:	Hinney, Anke, Nguyen, Thuy Trang, Scherag, André, Friedel, Susann, Brönner, Günter, Müller, Timo Dirk, Grallert, Harald, Illig, Thomas, Wichmann, H-Erich, Rief, Winfried, Schäfer, Helmut, Hebebrand, Johannes
Format:	Article
Language:	eng
Subjects:	Adipose Tissue - metabolism Adolescent Alpha-Ketoglutarate-Dependent Dioxygenase FTO Analysis Biometrics Body fat Body mass index Child Child & adolescent psychiatry Confidence intervals Creutzfeldt-Jakob disease Diabetes and Endocrinology/Obesity Diabetes and Endocrinology/Type 2 Diabetes Epidemiology Gene frequency Genes Genetic aspects Genetics and Genomics Genetics and Genomics/Complex Traits Genetics and Genomics/Gene Discovery Genetics and Genomics/Genetics of Disease Genetics and Genomics/Medical Genetics Genome, Human Genome-wide association studies Genomes Genomics Heritability Humans Linkage disequilibrium Obesity Obesity - genetics Offspring Organ Size Parents Polymorphism Polymorphism, Single Nucleotide Proteins - genetics Single nucleotide polymorphisms Single-nucleotide polymorphism Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Studies Type 2 diabetes
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Summary:	Obesity is a major health problem. Although heritability is substantial, genetic mechanisms predisposing to obesity are not very well understood. We have performed a genome wide association study (GWA) for early onset (extreme) obesity. a) GWA (Genome-Wide Human SNP Array 5.0 comprising 440,794 single nucleotide polymorphisms) for early onset extreme obesity based on 487 extremely obese young German individuals and 442 healthy lean German controls; b) confirmatory analyses on 644 independent families with at least one obese offspring and both parents. We aimed to identify and subsequently confirm the 15 SNPs (minor allele frequency > or =10%) with the lowest p-values of the GWA by four genetic models: additive, recessive, dominant and allelic. Six single nucleotide polymorphisms (SNPs) in FTO (fat mass and obesity associated gene) within one linkage disequilibrium (LD) block including the GWA SNP rendering the lowest p-value (rs1121980; log-additive model: nominal p = 1.13 x 10(-7), corrected p = 0.0494; odds ratio (OR)(CT) 1.67, 95% confidence interval (CI) 1.22-2.27; OR(TT) 2.76, 95% CI 1.88-4.03) belonged to the 15 SNPs showing the strongest evidence for association with obesity. For confirmation we genotyped 11 of these in the 644 independent families (of the six FTO SNPs we chose only two representing the LD bock). For both FTO SNPs the initial association was confirmed (both Bonferroni corrected p
ISSN:	1932-6203 1932-6203