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PMID: 17658951 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural

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

PLoS genetics ·Vol. 3 ·No. 7 ·2007-07-00 ·Pages e115

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

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.

MeSH Terms
Adiposity/genetics Adolescent Adult Aged Aged, 80 and over Alleles Alpha-Ketoglutarate-Dependent Dioxygenase FTO Body Mass Index Body Weight/genetics Female Genetic Predisposition to Disease Genetic Variation Genome, Human Humans Linkage Disequilibrium Male Middle Aged Obesity/genetics,pathology Phosphofructokinases/genetics Polymorphism, Single Nucleotide Proteins/genetics Quantitative Trait Loci
Chemicals
Proteins Alpha-Ketoglutarate-Dependent Dioxygenase FTO FTO protein, human Phosphofructokinases
Authors & Affiliations
25 authors, click to expand affiliations / ORCID
Scuteri Angelo
Unità Operativa Geriatria, Istituto per la Patologia Endocrina e Metabolica, Rome, Italy.
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
Conflict of Interest

Competing interests. The authors have declared that no competing interests exist.

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Article Info
Journal
PLoS genetics
Abbr.
PLoS Genet
ISSN
1553-7404
DOI
10.1371/journal.pgen.0030115
Published
2007-07-00
Pages
e115
Language
English
Region
United States
NLM ID
101239074
PMCID
PMC1934391
Subset
IM
Grants
NHLBI NIH HHS · U01 HL084729 · United States
NIA NIH HHS · N01-AG-1-2109 · United States
NHGRI NIH HHS · R01 HG002651 · United States
NHLBI NIH HHS · HL084729 · United States
Intramural NIH HHS · United States
PHS HHS · 263-MA-410953 · United States
NHGRI NIH HHS · HG02651 · United States
External Links
PubMed source DOI: 10.1371/journal.pgen.0030115 PMC Full Text View journal details
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