Genome-wide association study identifies two novel loci containing FLNB and SBF2 genes underlying stature variation

Shu Feng Lei, Li Jun Tan, Xiao Gang Liu, Liang Wang, Han Yan, Yan Fang Guo, Yao Zhong Liu, Dong Hai Xiong, Jian Li, Tie Lin Yang, Xiang Ding Chen, Yan Guo, Fei Yan Deng, Yin Ping Zhang, Xue Zhen Zhu, Shawn Levy, Christopher J. Papasian, James J. Hamilton, Robert R. Recker, Hong Wen Deng

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Abstract

Human stature, as an important physical index in clinical practice and a usual covariate in gene mapping of complex disorders, is a highly heritable complex trait. To identify specific genes underlying stature, a genome-wide association study was performed in 1000 unrelated homogeneous Caucasian subjects using Affymetrix 500K arrays. A group of seven contiguous markers in the region of SBF2 gene (Set-binding factor 2) are associated with stature, significantly so at the genome-wide level after false discovery rate (FDR) correction (FDR q = 0.034-0.042). Three SNPs in another SNP group in the Filamin B (FLNB) gene were also associated with stature, significantly so with FDR q = 0.042-0.048. In follow-up independent replication studies, rs10734652 in the SBF2 gene was significantly (P = 0.036) and suggestively (P = 0.07) associated with stature in Caucasian families and 1306 unrelated Caucasian subjects, respectively, and rs9834312 in the FLNB gene was also associated with stature in such two independent Caucasian populations (P = 0.008 in unrelated sample and P = 0.049 in family sample). Particularly, additional significant replication association signals were detected in Chinese, an ethnic population different from Caucasian, between rs9834312 and stature in 619 unrelated northern Chinese subjects (P = 0.017), as well as between rs10734652 and stature in 2953 unrelated southern Chinese subjects (P = 0.048). This study also provides additional replication evidence for some of the already published stature loci. These results, together with the known functional relevance of the SBF2 and FLNB genes to skeletal linear growth and bone formation, support that two regions containing FLNB and SBF2 genes are two novel loci underlying stature variation.

Original languageEnglish
Pages (from-to)1661-1669
Number of pages9
JournalHuman Molecular Genetics
Volume18
Issue number9
DOIs
StatePublished - 2009

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Filamins
Genome-Wide Association Study
Genes
Single Nucleotide Polymorphism
Chromosome Mapping
Osteogenesis
Population
Genome
Growth

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Genome-wide association study identifies two novel loci containing FLNB and SBF2 genes underlying stature variation. / Lei, Shu Feng; Tan, Li Jun; Liu, Xiao Gang; Wang, Liang; Yan, Han; Guo, Yan Fang; Liu, Yao Zhong; Xiong, Dong Hai; Li, Jian; Yang, Tie Lin; Chen, Xiang Ding; Guo, Yan; Deng, Fei Yan; Zhang, Yin Ping; Zhu, Xue Zhen; Levy, Shawn; Papasian, Christopher J.; Hamilton, James J.; Recker, Robert R.; Deng, Hong Wen.

In: Human Molecular Genetics, Vol. 18, No. 9, 2009, p. 1661-1669.

Research output: Contribution to journalArticle

Lei, SF, Tan, LJ, Liu, XG, Wang, L, Yan, H, Guo, YF, Liu, YZ, Xiong, DH, Li, J, Yang, TL, Chen, XD, Guo, Y, Deng, FY, Zhang, YP, Zhu, XZ, Levy, S, Papasian, CJ, Hamilton, JJ, Recker, RR & Deng, HW 2009, 'Genome-wide association study identifies two novel loci containing FLNB and SBF2 genes underlying stature variation', Human Molecular Genetics, vol. 18, no. 9, pp. 1661-1669. https://doi.org/10.1093/hmg/ddn405
Lei, Shu Feng ; Tan, Li Jun ; Liu, Xiao Gang ; Wang, Liang ; Yan, Han ; Guo, Yan Fang ; Liu, Yao Zhong ; Xiong, Dong Hai ; Li, Jian ; Yang, Tie Lin ; Chen, Xiang Ding ; Guo, Yan ; Deng, Fei Yan ; Zhang, Yin Ping ; Zhu, Xue Zhen ; Levy, Shawn ; Papasian, Christopher J. ; Hamilton, James J. ; Recker, Robert R. ; Deng, Hong Wen. / Genome-wide association study identifies two novel loci containing FLNB and SBF2 genes underlying stature variation. In: Human Molecular Genetics. 2009 ; Vol. 18, No. 9. pp. 1661-1669.
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abstract = "Human stature, as an important physical index in clinical practice and a usual covariate in gene mapping of complex disorders, is a highly heritable complex trait. To identify specific genes underlying stature, a genome-wide association study was performed in 1000 unrelated homogeneous Caucasian subjects using Affymetrix 500K arrays. A group of seven contiguous markers in the region of SBF2 gene (Set-binding factor 2) are associated with stature, significantly so at the genome-wide level after false discovery rate (FDR) correction (FDR q = 0.034-0.042). Three SNPs in another SNP group in the Filamin B (FLNB) gene were also associated with stature, significantly so with FDR q = 0.042-0.048. In follow-up independent replication studies, rs10734652 in the SBF2 gene was significantly (P = 0.036) and suggestively (P = 0.07) associated with stature in Caucasian families and 1306 unrelated Caucasian subjects, respectively, and rs9834312 in the FLNB gene was also associated with stature in such two independent Caucasian populations (P = 0.008 in unrelated sample and P = 0.049 in family sample). Particularly, additional significant replication association signals were detected in Chinese, an ethnic population different from Caucasian, between rs9834312 and stature in 619 unrelated northern Chinese subjects (P = 0.017), as well as between rs10734652 and stature in 2953 unrelated southern Chinese subjects (P = 0.048). This study also provides additional replication evidence for some of the already published stature loci. These results, together with the known functional relevance of the SBF2 and FLNB genes to skeletal linear growth and bone formation, support that two regions containing FLNB and SBF2 genes are two novel loci underlying stature variation.",
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AU - Lei, Shu Feng

AU - Tan, Li Jun

AU - Liu, Xiao Gang

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AU - Yan, Han

AU - Guo, Yan Fang

AU - Liu, Yao Zhong

AU - Xiong, Dong Hai

AU - Li, Jian

AU - Yang, Tie Lin

AU - Chen, Xiang Ding

AU - Guo, Yan

AU - Deng, Fei Yan

AU - Zhang, Yin Ping

AU - Zhu, Xue Zhen

AU - Levy, Shawn

AU - Papasian, Christopher J.

AU - Hamilton, James J.

AU - Recker, Robert R.

AU - Deng, Hong Wen

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N2 - Human stature, as an important physical index in clinical practice and a usual covariate in gene mapping of complex disorders, is a highly heritable complex trait. To identify specific genes underlying stature, a genome-wide association study was performed in 1000 unrelated homogeneous Caucasian subjects using Affymetrix 500K arrays. A group of seven contiguous markers in the region of SBF2 gene (Set-binding factor 2) are associated with stature, significantly so at the genome-wide level after false discovery rate (FDR) correction (FDR q = 0.034-0.042). Three SNPs in another SNP group in the Filamin B (FLNB) gene were also associated with stature, significantly so with FDR q = 0.042-0.048. In follow-up independent replication studies, rs10734652 in the SBF2 gene was significantly (P = 0.036) and suggestively (P = 0.07) associated with stature in Caucasian families and 1306 unrelated Caucasian subjects, respectively, and rs9834312 in the FLNB gene was also associated with stature in such two independent Caucasian populations (P = 0.008 in unrelated sample and P = 0.049 in family sample). Particularly, additional significant replication association signals were detected in Chinese, an ethnic population different from Caucasian, between rs9834312 and stature in 619 unrelated northern Chinese subjects (P = 0.017), as well as between rs10734652 and stature in 2953 unrelated southern Chinese subjects (P = 0.048). This study also provides additional replication evidence for some of the already published stature loci. These results, together with the known functional relevance of the SBF2 and FLNB genes to skeletal linear growth and bone formation, support that two regions containing FLNB and SBF2 genes are two novel loci underlying stature variation.

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