The majority of the genetic risk for Paget's disease of bone is explained by genetic variants close to the CSF1, OPTN, TM7SF4, and TNFRSF11A genes Pui Yan Jenny ChungGreet BeyensSteven BoonenSocrates PapapoulosPiet Geusens • Marcel KarperienFilip VanhoenackerLeon VerbruggenErik FransenJan Van Offel • Stefan GoemaereHans-Georg ZmierczakReneWesthovensJean-Pierre DevogelaerWim Van Hul

Paget's disease of bone (PDB) is one of the most frequent metabolic bone disorders (1-5%), next to osteo- porosis, affecting individuals above age 55. Sequestosome1 mutations explain a part of the PDB patients, but still the disease pathogenesis in the remaining PDB patients is lar- gely unknown. Therefore, association studies investigating the relationship between genetic polymorphisms and spo- radic PDB have been performed to find the genetic risk variants. Previously such studies indicated a role of the OPG and RANK gene. The latter was recently confirmed in a genome-wide association study (GWAS) which also indi- cated the involvement of chromosomal regions harbouring the CSF1 and OPTN gene. In this study, we sought to rep- licate these findings in a Belgian and a Dutch population. Similar significant results were obtained for the single nucleotide polymorphisms and the haplotypes. The most significant results are found in the CSF1 gene region, fol- lowed by the OPTN and TNFRSF11A gene region (p values ranging from 1.3 9 10 -4 to 3.8 9 10 -8 ,O R= 1.523-1.858). We next obtained significant association with