Tags

Type your tag names separated by a space and hit enter

Genome wide association (GWA) study for early onset extreme obesity supports the role of fat mass and obesity associated gene (FTO) variants.
PLoS One. 2007 Dec 26; 2(12):e1361.Plos

Abstract

BACKGROUND

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.

METHODOLOGY/PRINCIPAL FINDINGS

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<0.01). However, none of the nine non-FTO SNPs revealed significant transmission disequilibrium.

CONCLUSIONS/SIGNIFICANCE

Our GWA for extreme early onset obesity substantiates that variation in FTO strongly contributes to early onset obesity. This is a further proof of concept for GWA to detect genes relevant for highly complex phenotypes. We concurrently show that nine additional SNPs with initially low p-values in the GWA were not confirmed in our family study, thus suggesting that of the best 15 SNPs in the GWA only the FTO SNPs represent true positive findings.

Authors+Show Affiliations

Department of Child and Adolescent Psychiatry, University of Duisburg-Essen, Essen, Germany. anke.hinney@uni-due.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18159244

Citation

Hinney, Anke, et al. "Genome Wide Association (GWA) Study for Early Onset Extreme Obesity Supports the Role of Fat Mass and Obesity Associated Gene (FTO) Variants." PloS One, vol. 2, no. 12, 2007, pp. e1361.
Hinney A, Nguyen TT, Scherag A, et al. Genome wide association (GWA) study for early onset extreme obesity supports the role of fat mass and obesity associated gene (FTO) variants. PLoS ONE. 2007;2(12):e1361.
Hinney, A., Nguyen, T. T., Scherag, A., Friedel, S., Brönner, G., Müller, T. D., Grallert, H., Illig, T., Wichmann, H. E., Rief, W., Schäfer, H., & Hebebrand, J. (2007). Genome wide association (GWA) study for early onset extreme obesity supports the role of fat mass and obesity associated gene (FTO) variants. PloS One, 2(12), e1361.
Hinney A, et al. Genome Wide Association (GWA) Study for Early Onset Extreme Obesity Supports the Role of Fat Mass and Obesity Associated Gene (FTO) Variants. PLoS ONE. 2007 Dec 26;2(12):e1361. PubMed PMID: 18159244.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genome wide association (GWA) study for early onset extreme obesity supports the role of fat mass and obesity associated gene (FTO) variants. AU - Hinney,Anke, AU - Nguyen,Thuy Trang, AU - Scherag,André, AU - Friedel,Susann, AU - Brönner,Günter, AU - Müller,Timo Dirk, AU - Grallert,Harald, AU - Illig,Thomas, AU - Wichmann,H-Erich, AU - Rief,Winfried, AU - Schäfer,Helmut, AU - Hebebrand,Johannes, Y1 - 2007/12/26/ PY - 2007/07/12/received PY - 2007/12/04/accepted PY - 2007/12/27/pubmed PY - 2008/8/9/medline PY - 2007/12/27/entrez SP - e1361 EP - e1361 JF - PloS one JO - PLoS ONE VL - 2 IS - 12 N2 - BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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<0.01). However, none of the nine non-FTO SNPs revealed significant transmission disequilibrium. CONCLUSIONS/SIGNIFICANCE: Our GWA for extreme early onset obesity substantiates that variation in FTO strongly contributes to early onset obesity. This is a further proof of concept for GWA to detect genes relevant for highly complex phenotypes. We concurrently show that nine additional SNPs with initially low p-values in the GWA were not confirmed in our family study, thus suggesting that of the best 15 SNPs in the GWA only the FTO SNPs represent true positive findings. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/18159244/Genome_wide_association__GWA__study_for_early_onset_extreme_obesity_supports_the_role_of_fat_mass_and_obesity_associated_gene__FTO__variants_ L2 - http://dx.plos.org/10.1371/journal.pone.0001361 DB - PRIME DP - Unbound Medicine ER -