title: Common variants in a novel gene, FONG on chromosome 2q33.1 confer risk of osteoporosis in Japanese.
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.
authors.affiliation: Laboratory for Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, Tokyo, Japan.
authors.forename: Ikuyo
authors.initials: I
authors.lastname: Kou
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Urano
authors.forename: Naoshi
authors.initials: N
authors.lastname: Fukui
authors.forename: Hideki
authors.initials: H
authors.lastname: Ito
authors.forename: Kouichi
authors.initials: K
authors.lastname: Ozaki
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tanaka
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hosoi
authors.forename: Masataka
authors.initials: M
authors.lastname: Shiraki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Seijiro
authors.initials: S
authors.lastname: Mori
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D019877:Hydroxymethyl and Formyl Transferases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D007564:Japan; D015810:Linkage Disequilibrium / Q000235:genetics; D008875:Middle Aged; D010024:Osteoporosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D011506:Proteins; C560598:FTCDNL1 protein, human; D019877:Hydroxymethyl and Formyl Transferases