Genetic Pleiotropy of Bone-Related Phenotypes: Insights from Osteoporosis
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GENETICS (D KARASIK AND C ACKERT-BICKNELL, SECTION EDITORS)
Genetic Pleiotropy of Bone-Related Phenotypes: Insights from Osteoporosis M. A. Christou 1 & E. E. Ntzani 1,2 & D. Karasik 3,4
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose of Review We summarize recent evidence on the shared genetics within and outside the musculoskeletal system (mostly related to bone density and osteoporosis). Recent Findings Osteoporosis is determined by an interplay between multiple genetic and environmental factors. Significant progress has been made regarding its genetic background revealing a number of robustly validated loci and respective pathways. However, pleiotropic factors affecting bone and other tissues are not well understood. Summary The analytical methods proposed to test for potential associations between genetic variants and multiple phenotypes can be applied to bone-related data. A number of recent genetic studies have shown evidence of pleiotropy between bone density and other different phenotypes (traits, conditions, or diseases), within and outside the musculoskeletal system. Power benefits of combining correlated phenotypes, as well as unbiased discovery, make these studies promising. Studies in humans are supported by evidence from animal models. Drug development and repurposing should benefit from the pleiotropic approach. We believe that future studies should take into account shared genetics between the bone and related traits. Keywords Osteoporosis . Bone mineral density . BMD . Musculoskeletal . Genetic pleiotropy . GWAS
Introduction Osteoporosis is a common systemic skeletal disease characterized by reduced bone mass and impaired bone quality [1], leading to increased bone fragility and increased low-trauma fracture risk, especially in women and the elderly. Hip and vertebral This article is part of the Topical Collection on Genetics Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11914-020-00618-y) contains supplementary material, which is available to authorized users. * D. Karasik [email protected] 1
Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece
2
Center for Research Synthesis in Health, Department of Health Services, Policy and Practice, School of Public Health, Brown University, Providence, RI, USA
3
Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA
4
Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel
fractures are considered the archetypal osteoporotic fractures but the emerging significance of fractures at other sites augments the phenotypic variability of bone fragility. Bone fractures are very common and affect quality of life and productivity indices [2]; the 12-month mortality of osteoporotic fractures of the hip and spine can rise up to 20%. Bone mineral density (BMD) is a valuable biomarker of osteoporosis, although it represents only one of the
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