Common diseaseのGWAS １）骨粗鬆症

Genomic Study of Locomotive Diseases. Genome-wide association study for Osteoporosis.

　骨粗鬆症関連遺伝子多型を探索するGWASは，骨密度を指標に世界的規模で行われてきた。海外で施行された17件のGWASデータの大規模メタ解析では，骨密度と関連する56遺伝子座に位置する一塩基多型（SNP）が同定され，そのうち14遺伝子座に位置するSNPは脆弱性骨折とも関連していた。同定されたSNPの近傍にはRANKシグナルならびにWntシグナルに関わる遺伝子，あるいは間葉系幹細胞分化ならびに軟骨内骨化に関わる遺伝子など，骨粗鬆症との関わりが強く示唆される遺伝子が多数存在していた。我が国でも日本人を対象とするGWASによりFONG，WDSOF1，GPR98といった新規骨粗鬆症関連遺伝子が同定された。

　Numerous studies on genetic risks for osteoporosis have been performed to date, mainly using genome-wide association studies（GWAS）for assessing bone mineral density（BMD）as a quantitative trait, and recent large-scale meta-analyses of GWAS have identified a number of single nucleotide polymorphisms（SNPs）associated with low BMD or increased risk of fracture. Several of these SNPs cluster within the RANK signaling, mesenchymal stem cell differentiation, endochondral ossification, and Wnt signaling pathways. GWAS performed in Japanese populations also identified novel osteoporosis susceptibility genes such as FONG, WDSOF1 and GPR98. It is estimated that previously identified loci associated with BMD in total explain ～5％of the genetic variance for this trait. Some genetic risk scores based on BMD-decreasing alleles of the SNPs have been developed, however, their prediction ability for the risk of osteoporosis and fracture appears to be limited when BMD is known.