title: The fat mass and obesity associated gene, FTO, is also associated with osteoporosis phenotypes.
abstract: Obesity and osteoporosis are closely correlated genetically. FTO gene has been consistently identified to be associated with obesity phenotypes. A recent study reported that the mice lacking Fto could result in lower bone mineral density (BMD). Thus, we hypothesize that the FTO gene might be also important for osteoporosis phenotypes. To test for such a hypothesis, we performed an association analyses to investigate the relationship between SNPs in FTO and BMD at both hip and spine. A total of 141 SNPs were tested in two independent Chinese populations (818 and 809 unrelated Han subjects, respectively) and a Caucasian population (2,286 unrelated subjects). Combining the two Chinese samples, we identified 6 SNPs in FTO to be significantly associated with hip BMD after multiple testing adjustments, with the combined P values ranged from 4.99 × 10⁻⁴-1.47 × 10⁻⁴. These 6 SNPs are all located at the intron 8 of FTO and in high linkage disequilibrium. Each copy of the minor allele of each SNP was associated with increased hip BMD values with the effect size (beta) of ∼0.025 and ∼0.015 in the Chinese sample 1 and 2, respectively. However, none of these 6 SNPs showed significant association signal in the Caucasian sample, by presenting some extent of ethnic difference. Our findings, together with the prior biological evidence, suggest that the FTO gene might be a new candidate for BMD variation and osteoporosis in Chinese populations.
authors: Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, People's Republic of China.
authors: Yan
authors: Y
authors: Guo
authors: Hui
authors: H
authors: Liu
authors: Tie-Lin
authors: TL
authors: Yang
authors: Siyang M
authors: SM
authors: Li
authors: Siyuan K
authors: SK
authors: Li
authors: Qing
authors: Q
authors: Tian
authors: Yong-Jun
authors: YJ
authors: Liu
authors: Hong-Wen
authors: HW
authors: Deng
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D044466:Asian People / Q000235:genetics; D015519:Bone Density; D002681:China; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000208:ethnology / Q000235:genetics*; D010384:Pelvic Bones / Q000378:metabolism; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D013131:Spine / Q000378:metabolism; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human