A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus

Abstract

These results suggest that deletions in the 6p25.1 locus may predispose to higher risk of fracture in a subset of populations of European origin; larger and geographically restricted studies will be needed to confirm this regional association. This is a first step towards the evaluation of the role of rare CNVs in osteoporosis.

Copy number variations in 375 patients with oesophageal atresia and/or tracheoesophageal fistula

“…One de novo CNV (16p13.3 duplication, see Table 1) overlapped two inherited 16p13.3 duplications (see Table 3). We classified the rare CNVs as benign (45), uncertain -likely benign (106) and uncertain (7). Interestingly, we could classify nine CNVs as uncertain-likely pathogenic and two as pathogenic.…”

“…For instance, they can be ancestry-specific. 45 Inheritance of a single CNV from a healthy parent is generally a characteristic of a benign CNV. However, absence of distinct abnormalities in parents carrying the same rare CNV could, for instance, be explained by a subclinical phenotype in these parents, variable gene expressivity, incomplete penetrance, skewed X-inactivation and/or mutations elsewhere in the genome.…”

Quantitative imaging methods in osteoporosis

“…A high predicted risk justifies preventative treatment with anti-osteoporotic drugs. Although algorithms such as FRAX ® represent major advances in clinical practice, clinicians should be aware that these calculations do not accommodate all known risk factors and there are more fracture determinants remaining to be discovered (6)(7)(8). Although FRAX ® and the Garvan Fracture Risk Calculator provide estimates of which patients will sustain a fracture, these algorithms still underestimate observed fracture risk in at least half of patients (9).…”

Association of LRP5 Ala1330Val polymorphism with fracture risk: a meta-analysis

“…Their occurrence is influenced by many environmental factors, such as older age, low heel quantitative ultrasound stiffness index (<78%), history of fracture, recent falls, and failing of the chair test (Deng et al, 2015). In addition, genetic factors also play a key role in the pathogenesis of fractures (Oei et al, 2014;Gao et al, 2015).…”