Dissecting the Genetics of Osteoporosis using Systems Approaches. Issue 1 (January 2019)

• Record Type: Journal Article
• Authors: Al-Barghouthi, Basel M.; Farber, Charles R.
• Is Part Of: Trends in genetics. Volume 35:Issue 1(2019)
• Page Start: 55
• Page End: 67
• Publication Date: 2019-01
• Subjects: systems genetics -- osteoporosis -- genome-wide association study -- coexpression networks -- bone mineral density -- Bayesian networks; Genetics -- Periodicals; 576.5
• DOI: 10.1016/j.tig.2018.10.004
• Languages: English
• ISSNs: 0168-9525

Abstract

Abstract : Osteoporosis is a condition characterized by low bone mineral density (BMD) and an increased risk of fracture. Traits contributing to osteoporotic fracture are highly heritable, indicating that a comprehensive understanding of bone requires a thorough understanding of the genetic basis of bone traits. Towards this goal, genome-wide association studies (GWASs) have identified over 500 loci associated with bone traits. However, few of the responsible genes have been identified, and little is known of how these genes work together to influence systems-level bone function. In this review, we describe how systems genetics approaches can be used to fill these knowledge gaps. Highlights: Osteoporosis is a common, complex disease characterized by low bone mineral density (BMD). Quantitative bone traits influencing osteoporotic fracture, such as BMD, are highly heritable (h 2 > 0.5). Genome-wide association studies (GWASs) have identified >300 loci for BMD. However, most causal genes, their mechanisms of action, and how they interact are unknown. Systems genetics approaches can be used to integrate bone GWAS with other '-omics' data to identify causal variants and genes. Network-based analysis approaches can provide insight into how genetic variation impacts molecular networks and how network dysfunction leads to osteoporosis.