Is a gene important for bone resorption a candidate for obesity? An association and linkage study on the RANK (receptor activator of nuclear factor-κB) gene in a large Caucasian sample

Lan Juan Zhao, Yan Fang Guo, Dong Hai Xiong, Peng Xiao, Robert R. Recker, Hong Wen Deng

Research output: Contribution to journalArticle

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Abstract

In light of findings that osteoporosis and obesity may share some common genetic determination and previous reports that RANK (receptor activator of nuclear factor-κB) is expressed in skeletal muscles which are important for energy metabolism, we hypothesize that RANK, a gene essential for osteoclastogenesis, is also important for obesity. In order to test the hypothesis with solid data we first performed a linkage analysis around the RANK gene in 4,102 Caucasian subjects from 434 pedigrees, then we genotyped 19 SNPs in or around the RANK gene. A family-based association test (FBAT) was performed with both a quantitative measure of obesity [fat mass, lean mass, body mass index (BMI), and percentage fat mass (PFM)] and a dichotomously defined obesity phenotype-OB (OB if BMI ≥ 30kg/m2). In the linkage analysis, an empirical P = 0.004 was achieved at the location of the RANK gene for BMI. Family-based association analysis revealed significant associations of eight SNPs with at least one obesity-related phenotype (P <0.05). Evidence of association was obtained at SNP10 (P = 0.002) and SNP16 (P = 0.001) with OB; SNP1 with fat mass (P = 0.003) SNP1 (P = 0.003) and SNP7 (P = 0.003) with lean mass; SNP1 (P = 0.002) and SNP7 (P = 0.002) with BMI; SNP1 (P = 0.003), SNP4 (P = 0.007), and SNP7 (P = 0.002) with PFM. In order to deal with the complex multiple testing issues, we performed FBAT multi-marker test (FBAT-MM) to evaluate the association between all the 18 SNPs and each obesity phenotype. The P value is 0.126 for OB, 0.033 for fat mass, 0.021 for lean mass, 0.016 for BMI, and 0.006 for PFM. The haplotype data analyses provide further association evidence. In conclusion, for the first time, our results suggest that RANK is a novel candidate for determination of obesity.

Original languageEnglish
Pages (from-to)561-570
Number of pages10
JournalHuman Genetics
Volume120
Issue number4
DOIs
StatePublished - Nov 2006

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Bone Resorption
Cytoplasmic and Nuclear Receptors
Obesity
Fats
Body Mass Index
Genes
Single Nucleotide Polymorphism
Phenotype
Essential Genes
Pedigree
Osteogenesis
Haplotypes
Energy Metabolism
Osteoporosis
Skeletal Muscle

All Science Journal Classification (ASJC) codes

  • Genetics(clinical)
  • Genetics

Cite this

Is a gene important for bone resorption a candidate for obesity? An association and linkage study on the RANK (receptor activator of nuclear factor-κB) gene in a large Caucasian sample. / Zhao, Lan Juan; Guo, Yan Fang; Xiong, Dong Hai; Xiao, Peng; Recker, Robert R.; Deng, Hong Wen.

In: Human Genetics, Vol. 120, No. 4, 11.2006, p. 561-570.

Research output: Contribution to journalArticle

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abstract = "In light of findings that osteoporosis and obesity may share some common genetic determination and previous reports that RANK (receptor activator of nuclear factor-κB) is expressed in skeletal muscles which are important for energy metabolism, we hypothesize that RANK, a gene essential for osteoclastogenesis, is also important for obesity. In order to test the hypothesis with solid data we first performed a linkage analysis around the RANK gene in 4,102 Caucasian subjects from 434 pedigrees, then we genotyped 19 SNPs in or around the RANK gene. A family-based association test (FBAT) was performed with both a quantitative measure of obesity [fat mass, lean mass, body mass index (BMI), and percentage fat mass (PFM)] and a dichotomously defined obesity phenotype-OB (OB if BMI ≥ 30kg/m2). In the linkage analysis, an empirical P = 0.004 was achieved at the location of the RANK gene for BMI. Family-based association analysis revealed significant associations of eight SNPs with at least one obesity-related phenotype (P <0.05). Evidence of association was obtained at SNP10 (P = 0.002) and SNP16 (P = 0.001) with OB; SNP1 with fat mass (P = 0.003) SNP1 (P = 0.003) and SNP7 (P = 0.003) with lean mass; SNP1 (P = 0.002) and SNP7 (P = 0.002) with BMI; SNP1 (P = 0.003), SNP4 (P = 0.007), and SNP7 (P = 0.002) with PFM. In order to deal with the complex multiple testing issues, we performed FBAT multi-marker test (FBAT-MM) to evaluate the association between all the 18 SNPs and each obesity phenotype. The P value is 0.126 for OB, 0.033 for fat mass, 0.021 for lean mass, 0.016 for BMI, and 0.006 for PFM. The haplotype data analyses provide further association evidence. In conclusion, for the first time, our results suggest that RANK is a novel candidate for determination of obesity.",
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AU - Xiao, Peng

AU - Recker, Robert R.

AU - Deng, Hong Wen

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