Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits.

Angelo Scuteri, Serena Sanna, Wei Min Chen, Manuela Uda, Giuseppe Albai, James Strait, Samer Najjar, Ramaiah Nagaraja, Marco Orrú, Gianluca Usala, Mariano Dei, Sandra Lai, Andrea Maschio, Fabio Busonero, Antonella Mulas, Georg B. Ehret, Ashley A. Fink, Alan B. Weder, Richard S. Cooper, Pilar GalanAravinda Chakravarti, David Schlessinger, Antonio Cao, Edward Lakatta, Gonçalo R. Abecasis

Research output: Contribution to journalArticle

Abstract

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 and Hispanic American follow-up samples, p = 0.001), weight (p = 0.001), and hip circumference (p = 0.0005). We did not replicate association between rs6602024 and obesity-related traits in the GenNet sample, although we found that in European Americans, Hispanic Americans, and African Americans, homozygotes for the rare "A" allele were, on average, 1.0-3.0 BMI units heavier than homozygotes for the more common "G" allele. In summary, we have completed a whole genome-association scan for three obesity-related quantitative traits and report that common genetic variants in the FTO gene are associated with substantial changes in BMI, hip circumference, and body weight. These changes could have a significant impact on the risk of obesity-related morbidity in the general population.

Original languageEnglish (US)
JournalPLoS Genetics
Volume3
Issue number7
DOIs
StatePublished - Jul 2007

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obesity
Genome-Wide Association Study
Homozygote
homozygosity
allele
genome
Hispanic Americans
Obesity
Alleles
hips
alleles
Single Nucleotide Polymorphism
Hip
gene
Genes
genes
Sardinia
quantitative traits
Weights and Measures
Gene Frequency

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. / Scuteri, Angelo; Sanna, Serena; Chen, Wei Min; Uda, Manuela; Albai, Giuseppe; Strait, James; Najjar, Samer; Nagaraja, Ramaiah; Orrú, Marco; Usala, Gianluca; Dei, Mariano; Lai, Sandra; Maschio, Andrea; Busonero, Fabio; Mulas, Antonella; Ehret, Georg B.; Fink, Ashley A.; Weder, Alan B.; Cooper, Richard S.; Galan, Pilar; Chakravarti, Aravinda; Schlessinger, David; Cao, Antonio; Lakatta, Edward; Abecasis, Gonçalo R.

In: PLoS Genetics, Vol. 3, No. 7, 07.2007.

Research output: Contribution to journalArticle

Scuteri, A, Sanna, S, Chen, WM, Uda, M, Albai, G, Strait, J, Najjar, S, Nagaraja, R, Orrú, M, Usala, G, Dei, M, Lai, S, Maschio, A, Busonero, F, Mulas, A, Ehret, GB, Fink, AA, Weder, AB, Cooper, RS, Galan, P, Chakravarti, A, Schlessinger, D, Cao, A, Lakatta, E & Abecasis, GR 2007, 'Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits.', PLoS Genetics, vol. 3, no. 7. https://doi.org/10.1371/journal.pgen.0030115
Scuteri, Angelo ; Sanna, Serena ; Chen, Wei Min ; Uda, Manuela ; Albai, Giuseppe ; Strait, James ; Najjar, Samer ; Nagaraja, Ramaiah ; Orrú, Marco ; Usala, Gianluca ; Dei, Mariano ; Lai, Sandra ; Maschio, Andrea ; Busonero, Fabio ; Mulas, Antonella ; Ehret, Georg B. ; Fink, Ashley A. ; Weder, Alan B. ; Cooper, Richard S. ; Galan, Pilar ; Chakravarti, Aravinda ; Schlessinger, David ; Cao, Antonio ; Lakatta, Edward ; Abecasis, Gonçalo R. / Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. In: PLoS Genetics. 2007 ; Vol. 3, No. 7.
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title = "Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits.",
abstract = "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 and Hispanic American follow-up samples, p = 0.001), weight (p = 0.001), and hip circumference (p = 0.0005). We did not replicate association between rs6602024 and obesity-related traits in the GenNet sample, although we found that in European Americans, Hispanic Americans, and African Americans, homozygotes for the rare {"}A{"} allele were, on average, 1.0-3.0 BMI units heavier than homozygotes for the more common {"}G{"} allele. In summary, we have completed a whole genome-association scan for three obesity-related quantitative traits and report that common genetic variants in the FTO gene are associated with substantial changes in BMI, hip circumference, and body weight. These changes could have a significant impact on the risk of obesity-related morbidity in the general population.",
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T1 - Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits.

AU - Scuteri, Angelo

AU - Sanna, Serena

AU - Chen, Wei Min

AU - Uda, Manuela

AU - Albai, Giuseppe

AU - Strait, James

AU - Najjar, Samer

AU - Nagaraja, Ramaiah

AU - Orrú, Marco

AU - Usala, Gianluca

AU - Dei, Mariano

AU - Lai, Sandra

AU - Maschio, Andrea

AU - Busonero, Fabio

AU - Mulas, Antonella

AU - Ehret, Georg B.

AU - Fink, Ashley A.

AU - Weder, Alan B.

AU - Cooper, Richard S.

AU - Galan, Pilar

AU - Chakravarti, Aravinda

AU - Schlessinger, David

AU - Cao, Antonio

AU - Lakatta, Edward

AU - Abecasis, Gonçalo R.

PY - 2007/7

Y1 - 2007/7

N2 - 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 and Hispanic American follow-up samples, p = 0.001), weight (p = 0.001), and hip circumference (p = 0.0005). We did not replicate association between rs6602024 and obesity-related traits in the GenNet sample, although we found that in European Americans, Hispanic Americans, and African Americans, homozygotes for the rare "A" allele were, on average, 1.0-3.0 BMI units heavier than homozygotes for the more common "G" allele. In summary, we have completed a whole genome-association scan for three obesity-related quantitative traits and report that common genetic variants in the FTO gene are associated with substantial changes in BMI, hip circumference, and body weight. These changes could have a significant impact on the risk of obesity-related morbidity in the general population.

AB - 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 and Hispanic American follow-up samples, p = 0.001), weight (p = 0.001), and hip circumference (p = 0.0005). We did not replicate association between rs6602024 and obesity-related traits in the GenNet sample, although we found that in European Americans, Hispanic Americans, and African Americans, homozygotes for the rare "A" allele were, on average, 1.0-3.0 BMI units heavier than homozygotes for the more common "G" allele. In summary, we have completed a whole genome-association scan for three obesity-related quantitative traits and report that common genetic variants in the FTO gene are associated with substantial changes in BMI, hip circumference, and body weight. These changes could have a significant impact on the risk of obesity-related morbidity in the general population.

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