title: FTO polymorphisms are associated with obesity but not diabetes risk in postmenopausal women.
abstract: The FTO gene was recently identified as a susceptibility locus for both obesity and type 2 diabetes by whole-genome association analyses of several European populations. We tested for an association between FTO risk alleles and obesity and diabetes in a well-characterized multiethnic cohort of postmenopausal women in the United States. We genotyped two most significantly associated single-nucleotide polymorphisms (SNPs) (rs9939609 and rs8050136) in intron 1 of FTO gene in a nested case-control study of 1,517 diabetes cases and 2,123 controls from the Women's Health Initiative-Observational Study (WHI-OS). The allelic frequencies of either rs9939609 or rs8050136 differed widely across four ethnic groups. The frequency of the rare allele A of rs9939609 among controls was much lower in Asians/Pacific Islanders (17%) than in blacks (45%), whites (40%), and Hispanics (31%). We found significant associations of rs9939609 with BMI and waist circumference in white and Hispanic women, but not among black and Asian/Pacific Islander women. On average, each copy of the risk-allele A at rs9939609 was significantly associated with 0.45 kg/m(2) increase in BMI (95% confidence interval (CI): 0.16-0.74; P = 0.004) and 0.97 cm increase in waist circumference (95% CI: 0.21-0.65; P = 0.0002). Similar results were observed for rs8050136. However, we found no significant genetic associations with diabetes risk, either within the full study sample or in any ethnic group. In conclusion, common genetic variants in the intron 1 of FTO gene may confer a modest susceptibility to obesity in an ethnicity-specific manner, but may be unlikely to contribute to a clinically significant diabetes risk.
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Song
authors.forename: Nai-Chieh
authors.initials: NC
authors.lastname: You
authors.forename: Yi-Hsiang
authors.initials: YH
authors.lastname: Hsu
authors.forename: Barbara V
authors.initials: BV
authors.lastname: Howard
authors.forename: Robert D
authors.initials: RD
authors.lastname: Langer
authors.forename: Joann E
authors.initials: JE
authors.lastname: Manson
authors.forename: Lauren
authors.initials: L
authors.lastname: Nathan
authors.forename: Tianhua
authors.initials: T
authors.lastname: Niu
authors.forename: Lesley
authors.initials: L
authors.lastname: F Tinker
authors.forename: Simin
authors.initials: S
authors.lastname: Liu
mesh_terms: D000368:Aged; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D016022:Case-Control Studies; D003920:Diabetes Mellitus / Q000208:ethnology / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D009765:Obesity / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017698:Postmenopause; D011506:Proteins / Q000235:genetics*; D014481:United States; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human
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