Common variants in a novel gene, FONG on chromosome 2q33.1 confer risk of osteoporosis in Japanese

Ikuyo Kou, Atsushi Takahashi, Tomohiko Urano, Naoshi Fukui, Hideki Ito, Kouichi Ozaki, Toshihiro Tanaka, Takayuki Hosoi, Masataka Shiraki, Satoshi Inoue, Yusuke Nakamura, Naoyuki Kamatani, Michiaki Kubo, Seijiro Mori, Shiro Ikegawa

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Osteoporosis is a common disease characterized by low bone mass, decreased bone quality and increased predisposition to fracture. Genetic factors have been implicated in its etiology; however, the specific genes related to susceptibility to osteoporosis are not entirely known. To detect susceptibility genes for osteoporosis, we conducted a genome-wide association study in Japanese using ~270,000 SNPs in 1,747 subjects (190 cases and 1,557 controls) followed by multiple levels of replication of the association using a total of ~5,000 subjects (2,092 cases and 3,114 controls). Through these staged association studies followed by resequencing and linkage disequilibrium mapping, we identified a single nucleotide polymorphism (SNP), rs7605378 associated with osteoporosis. (combined P = 1.51×10 -8 , odds ratio = 1.25). This SNP is in a previously unknown gene on chromosome 2q33.1, FONG. FONG is predicted to encode a 147 amino-acid protein with a formiminotransferase domain in its N-terminal (FTCD_N domain) and is ubiquitously expressed in various tissues including bone. Our findings would give a new insight into osteoporosis etiology and pathogenesis.

Original languageEnglish
Article numbere19641
JournalPloS one
Volume6
Issue number5
DOIs
Publication statusPublished - 16-05-2011

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osteoporosis
Chromosomes
Osteoporosis
Genes
chromosomes
Bone
Single Nucleotide Polymorphism
Polymorphism
bones
genes
Nucleotides
Bone and Bones
hydroxymethyltransferases and formyltransferases
single nucleotide polymorphism
etiology
Chromosome Mapping
Genome-Wide Association Study
Linkage Disequilibrium
linkage disequilibrium
odds ratio

All Science Journal Classification (ASJC) codes

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

Cite this

Kou, I., Takahashi, A., Urano, T., Fukui, N., Ito, H., Ozaki, K., ... Ikegawa, S. (2011). Common variants in a novel gene, FONG on chromosome 2q33.1 confer risk of osteoporosis in Japanese. PloS one, 6(5), [e19641]. https://doi.org/10.1371/journal.pone.0019641
Kou, Ikuyo ; Takahashi, Atsushi ; Urano, Tomohiko ; Fukui, Naoshi ; Ito, Hideki ; Ozaki, Kouichi ; Tanaka, Toshihiro ; Hosoi, Takayuki ; Shiraki, Masataka ; Inoue, Satoshi ; Nakamura, Yusuke ; Kamatani, Naoyuki ; Kubo, Michiaki ; Mori, Seijiro ; Ikegawa, Shiro. / Common variants in a novel gene, FONG on chromosome 2q33.1 confer risk of osteoporosis in Japanese. In: PloS one. 2011 ; Vol. 6, No. 5.
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abstract = "Osteoporosis is a common disease characterized by low bone mass, decreased bone quality and increased predisposition to fracture. Genetic factors have been implicated in its etiology; however, the specific genes related to susceptibility to osteoporosis are not entirely known. To detect susceptibility genes for osteoporosis, we conducted a genome-wide association study in Japanese using ~270,000 SNPs in 1,747 subjects (190 cases and 1,557 controls) followed by multiple levels of replication of the association using a total of ~5,000 subjects (2,092 cases and 3,114 controls). Through these staged association studies followed by resequencing and linkage disequilibrium mapping, we identified a single nucleotide polymorphism (SNP), rs7605378 associated with osteoporosis. (combined P = 1.51×10 -8 , odds ratio = 1.25). This SNP is in a previously unknown gene on chromosome 2q33.1, FONG. FONG is predicted to encode a 147 amino-acid protein with a formiminotransferase domain in its N-terminal (FTCD_N domain) and is ubiquitously expressed in various tissues including bone. Our findings would give a new insight into osteoporosis etiology and pathogenesis.",
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Kou, I, Takahashi, A, Urano, T, Fukui, N, Ito, H, Ozaki, K, Tanaka, T, Hosoi, T, Shiraki, M, Inoue, S, Nakamura, Y, Kamatani, N, Kubo, M, Mori, S & Ikegawa, S 2011, 'Common variants in a novel gene, FONG on chromosome 2q33.1 confer risk of osteoporosis in Japanese', PloS one, vol. 6, no. 5, e19641. https://doi.org/10.1371/journal.pone.0019641

Common variants in a novel gene, FONG on chromosome 2q33.1 confer risk of osteoporosis in Japanese. / Kou, Ikuyo; Takahashi, Atsushi; Urano, Tomohiko; Fukui, Naoshi; Ito, Hideki; Ozaki, Kouichi; Tanaka, Toshihiro; Hosoi, Takayuki; Shiraki, Masataka; Inoue, Satoshi; Nakamura, Yusuke; Kamatani, Naoyuki; Kubo, Michiaki; Mori, Seijiro; Ikegawa, Shiro.

In: PloS one, Vol. 6, No. 5, e19641, 16.05.2011.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Common variants in a novel gene, FONG on chromosome 2q33.1 confer risk of osteoporosis in Japanese

AU - Kou, Ikuyo

AU - Takahashi, Atsushi

AU - Urano, Tomohiko

AU - Fukui, Naoshi

AU - Ito, Hideki

AU - Ozaki, Kouichi

AU - Tanaka, Toshihiro

AU - Hosoi, Takayuki

AU - Shiraki, Masataka

AU - Inoue, Satoshi

AU - Nakamura, Yusuke

AU - Kamatani, Naoyuki

AU - Kubo, Michiaki

AU - Mori, Seijiro

AU - Ikegawa, Shiro

PY - 2011/5/16

Y1 - 2011/5/16

N2 - Osteoporosis is a common disease characterized by low bone mass, decreased bone quality and increased predisposition to fracture. Genetic factors have been implicated in its etiology; however, the specific genes related to susceptibility to osteoporosis are not entirely known. To detect susceptibility genes for osteoporosis, we conducted a genome-wide association study in Japanese using ~270,000 SNPs in 1,747 subjects (190 cases and 1,557 controls) followed by multiple levels of replication of the association using a total of ~5,000 subjects (2,092 cases and 3,114 controls). Through these staged association studies followed by resequencing and linkage disequilibrium mapping, we identified a single nucleotide polymorphism (SNP), rs7605378 associated with osteoporosis. (combined P = 1.51×10 -8 , odds ratio = 1.25). This SNP is in a previously unknown gene on chromosome 2q33.1, FONG. FONG is predicted to encode a 147 amino-acid protein with a formiminotransferase domain in its N-terminal (FTCD_N domain) and is ubiquitously expressed in various tissues including bone. Our findings would give a new insight into osteoporosis etiology and pathogenesis.

AB - Osteoporosis is a common disease characterized by low bone mass, decreased bone quality and increased predisposition to fracture. Genetic factors have been implicated in its etiology; however, the specific genes related to susceptibility to osteoporosis are not entirely known. To detect susceptibility genes for osteoporosis, we conducted a genome-wide association study in Japanese using ~270,000 SNPs in 1,747 subjects (190 cases and 1,557 controls) followed by multiple levels of replication of the association using a total of ~5,000 subjects (2,092 cases and 3,114 controls). Through these staged association studies followed by resequencing and linkage disequilibrium mapping, we identified a single nucleotide polymorphism (SNP), rs7605378 associated with osteoporosis. (combined P = 1.51×10 -8 , odds ratio = 1.25). This SNP is in a previously unknown gene on chromosome 2q33.1, FONG. FONG is predicted to encode a 147 amino-acid protein with a formiminotransferase domain in its N-terminal (FTCD_N domain) and is ubiquitously expressed in various tissues including bone. Our findings would give a new insight into osteoporosis etiology and pathogenesis.

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