Impact of the environment on the skeleton: Is it modulated by genetic factors?

Cheryl L. Ackert-Bicknell, David Karasik

Research output: Contribution to journalArticlepeer-review

Abstract

The etiology of skeletal disease is driven by genetic and environmental factors. Genome-wide association studies (GWAS) of osteoporotic phenotypes have identified novel candidate genes, but have only uncovered a small proportion of the trait variance explained. This "missing heritability" is caused by several factors, including the failure to consider gene-by-environmental (G*E) interactions. Some G*E interactions have been investigated, but new approaches to integrate environmental data into genomic studies are needed. Advances in genotyping and meta-analysis techniques now allow combining genotype data from multiple studies, but the measurement of key environmental factors in large human cohorts still lags behind, as do the statistical tools needed to incorporate these measures in genome-wide association meta-studies. This review focuses on discussing ways to enhance G*E interaction studies in humans and how the use of rodent models can inform genetic studies. Understanding G*E interactions will provide opportunities to effectively target intervention strategies for individualized therapy.

Original languageEnglish
Pages (from-to)219-228
Number of pages10
JournalCurrent Osteoporosis Reports
Volume11
Issue number3
DOIs
StatePublished - Sep 2013

Keywords

  • Bone mineral density
  • Candidate gene
  • Collaborative cross
  • Congenic strains
  • Diversity outcross
  • Fracture
  • Gene-by-environment interactions
  • Genome-wide association studies
  • Osteoporosis
  • Rodent models
  • Transgenic mice

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism

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