Powerful bivariate Genome-wide association analyses suggest the SOX6 gene influencing both obesity and osteoporosis phenotypes in males

Yao Zhong Liu, Yu Fang Pei, Jian Feng Liu, Fang Yang, Yan Guo, Lei Zhang, Xiao Gang Liu, Han Yan, Liang Wang, Yin Ping Zhang, Shawn Levy, Robert R. Recker, Hong Wen Deng

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Abstract

Background: Current genome-wide association studies (GWAS) are normally implemented in a univariate framework and analyze different phenotypes in isolation. This univariate approach ignores the potential genetic correlation between important disease traits. Hence this approach is difficult to detect pleiotropic genes, which may exist for obesity and osteoporosis, two common diseases of major public health importance that are closely correlated genetically. Principal Findings: To identify such pleiotropic genes and the key mechanistic links between the two diseases, we here performed the first bivariate GWAS of obesity and osteoporosis. We searched for genes underlying co-variation of the obesity phenotype, body mass index (BMI), with the osteoporosis risk phenotype, hip bone mineral density (BMD), scanning ∼380,000 SNPs in 1,000 unrelated homogeneous Caucasians, including 499 males and 501 females. We identified in the male subjects two SNPs in intron 1 of the SOX6 (SRY-box 6) gene, rs297325 and rs4756846, which were bivariately associated with both BMI and hip BMD, achieving p values of 6.82×10-7 and 1.47×10-6, respectively. The two SNPs ranked at the top in significance for bivariate association with BMI and hip BMD in the male subjects among all the ∼380,000 SNPs examined genome-wide. The two SNPs were replicated in a Framingham Heart Study (FHS) cohort containing 3,355 Caucasians (1,370 males and 1,985 females) from 975 families. In the FHS male subjects, the two SNPs achieved p values of 0.03 and 0.02, respectively, for bivariate association with BMI and femoral neck BMD. Interestingly, SOX6 was previously found to be essential to both cartilage formation/chondrogenesis and obesity-related insulin resistance, suggesting the gene's dual role in both bone and fat. Conclusions: Our findings, together with the prior biological evidence, suggest the SOX6 gene's importance in coregulation of obesity and osteoporosis.

Original languageEnglish
Article numbere6827
JournalPLoS One
Volume4
Issue number8
DOIs
StatePublished - Aug 28 2009

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Genome-Wide Association Study
osteoporosis
Osteoporosis
Single Nucleotide Polymorphism
obesity
Obesity
Genes
bone density
Pelvic Bones
Phenotype
phenotype
Bone Density
genome
body mass index
Body Mass Index
Genetic Pleiotropy
hips
Bone
Minerals
genes

All Science Journal Classification (ASJC) codes

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Powerful bivariate Genome-wide association analyses suggest the SOX6 gene influencing both obesity and osteoporosis phenotypes in males. / Liu, Yao Zhong; Pei, Yu Fang; Liu, Jian Feng; Yang, Fang; Guo, Yan; Zhang, Lei; Liu, Xiao Gang; Yan, Han; Wang, Liang; Zhang, Yin Ping; Levy, Shawn; Recker, Robert R.; Deng, Hong Wen.

In: PLoS One, Vol. 4, No. 8, e6827, 28.08.2009.

Research output: Contribution to journalArticle

Liu, YZ, Pei, YF, Liu, JF, Yang, F, Guo, Y, Zhang, L, Liu, XG, Yan, H, Wang, L, Zhang, YP, Levy, S, Recker, RR & Deng, HW 2009, 'Powerful bivariate Genome-wide association analyses suggest the SOX6 gene influencing both obesity and osteoporosis phenotypes in males', PLoS One, vol. 4, no. 8, e6827. https://doi.org/10.1371/journal.pone.0006827
Liu, Yao Zhong ; Pei, Yu Fang ; Liu, Jian Feng ; Yang, Fang ; Guo, Yan ; Zhang, Lei ; Liu, Xiao Gang ; Yan, Han ; Wang, Liang ; Zhang, Yin Ping ; Levy, Shawn ; Recker, Robert R. ; Deng, Hong Wen. / Powerful bivariate Genome-wide association analyses suggest the SOX6 gene influencing both obesity and osteoporosis phenotypes in males. In: PLoS One. 2009 ; Vol. 4, No. 8.
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AU - Liu, Xiao Gang

AU - Yan, Han

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