Open AccessCommon Variants in a Novel Gene, FONG on Chromosome 2q33.1 Confer Risk of Osteoporosis in Japanese
Author(s) -
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
Publication year - 2011
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0019641
Subject(s) - single nucleotide polymorphism , genetics , snp , osteoporosis , linkage disequilibrium , genome wide association study , genetic association , biology , haplotype , genetic predisposition , odds ratio , bioinformatics , medicine , gene , allele , genotype , endocrinology
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.