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6% in the GenePage cohort. The relation between PDB susceptibility alleles, disease extent, and complications in 688 subjects from the PRISM cohort who tested negative for SQSTM1 mutations are shown in Table 1. There was a significant association between risk allele score and number of affected bones with evidence of http://www.selleckchem.com/products/azd9291.html an allele dose effect (p?=?0.04). A similar trend was observed for disease severity score, but the differences were not significant. Family history of PDB was significantly associated with risk allele score in this subgroup of patients (p?=?0.01) as was the number of previous courses of bisphosphonates received for PDB (p?=?0.04). There was no significant association between allele risk score and sex, age, age at diagnosis of PDB, quality-of-life measures, the presence of deafness owing to PDB (reflected by use of a hearing aid and skull involvement), fractures through Pagetic bone, orthopedic surgery, or bone deformity. To determine if risk alleles were associated with disease severity in other populations, we employed meta-analysis to examine the relation between risk allele score and markers of disease severity in SQSTM1-negative subjects from all http://www.selleck.cn/products/Everolimus(RAD001).html centers. This showed a highly significant association between risk allele score and both disease extent and severity with evidence of an allele dose effect. The number of affected bones was significantly greater in tertile 2 compared with tertile 1 (standardized mean difference 0.20 http://www.selleckchem.com/products/ch5424802.html [0.08�C0.31], p?=?0.0007) and greater still in tertile 3 compared with tertile 1 (standardized mean difference 0.27 [0.15�C0.38], p?=?0.00001) (Fig. 2). A similar effect was noted for disease severity score, which was greater in tertile 2 than in tertile 1 (0.15 [0.03�C0.26], p?=?0.01) and greater still in tertile 3 compared with tertile 1 (0.25 [0.13�C0.36], p?