Genetics of osteosarcopenia

Iryna Khrystoforova, Ching Ti Liu, David Karasik

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


Purpose of review To summarize the evidence from recent studies on the genetic contributions to the etiology of osteosarcopenia (OSP), mostly based on genomic studies in bone and muscle, in humans, and in animal models. Recent findings Genome-wide association studies (GWAS) have successfully identified multiple loci overlapping between the bone and muscle parameters used for OSP diagnosis. Joint analyses of multiple correlated musculoskeletal traits (i.e., multivariate GWAS) have underscored multiple genes with possible pleiotropic effects on both bone and muscle. Several of the proposed pleiotropic genes have been validated using human cells or animal models. Summary Current challenges include: absence of clear definition/diagnosis; lack of GWAS focused on the aged population; and lacking functional annotation for a majority of identified variants and loci. However, the potential of genomic discovery, especially pleiotropic factors affecting bone and muscle tissues, is not fully realized for refining the OSP diagnosis and in targeted interventions. Power benefits of combining correlated phenotypes, as well as unbiased discovery, make the pleiotropic GWAS studies promising. Drug development and repurposing should benefit from the integrative approach. We believe that future studies should focus on the population of risk for OSP, in parallel with applying sophisticated phenotyping.

Original languageEnglish
Title of host publicationOsteosarcopenia
Number of pages22
ISBN (Electronic)9780128200889
ISBN (Print)9780128204207
StatePublished - 1 Jan 2022

Bibliographical note

Publisher Copyright:
© 2022 Elsevier Inc. All rights reserved.


  • Animal models
  • Bone
  • Functional validation
  • GWAS
  • Muscle
  • Osteoporosis
  • Pleiotropy
  • Sarcopenia


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