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

• Published in: PloS one 2011-05, Vol.6 (5), p.e19641-e19641
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino acids; Arthritis; Asian Continental Ancestry Group - genetics; Base Sequence; Binding sites; Biocompatibility; Biology; Bone mass; Chromosome 2; Chromosome Mapping; Chromosomes, Human, Pair 2 - genetics; Disease susceptibility; Etiology; Female; Gene Expression Profiling; Gene Expression Regulation; Gene mapping; Genes; Genetic aspects; Genetic factors; Genetic Predisposition to Disease; Genetic Testing; Genetics, Population; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genomics; Geriatrics; Haplotypes; Haplotypes - genetics; Heart attacks; Homeostasis; Hospitals; Humans; Hydroxymethyl and Formyl Transferases - chemistry; Hydroxymethyl and Formyl Transferases - genetics; Hydroxymethyl and Formyl Transferases - metabolism; Hypotheses; Internal medicine; Japan; Kinases; Laboratories; Linkage disequilibrium; Linkage Disequilibrium - genetics; Medicine; MicroRNAs; Middle Aged; Osteoporosis; Osteoporosis - genetics; Pathogenesis; Polymorphism; Polymorphism, Single Nucleotide - genetics; Population; Principal components analysis; Proteins - chemistry; Proteins - genetics; Proteins - metabolism; Risk factors; Signal transduction; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Statistical analysis; Studies; Tissues
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0019641

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.