Family-based genetic analysis of osteoporosis

Abstract

Osteoporosis is a common disease affecting a significant proportion of older people. Its primary endpoint, fracture, results in severe outcomes including increased morbidity and early mortality. Bone mineral density (BMD) and quantitative ultrasound (QUS), both quantitative traits, are strong predictors of osteoporosis and fracture risk. Furthermore, they, along with osteoporosis and fracture, have been shown to be under genetic influence, indicating that quantitative trait loci (QTLs) may be responsible for the variation observed in each of these traits. In this thesis, I used data from the Dubbo Osteoporosis Genetics Study – a large family-based study – together with data from the Dubbo Osteoporosis Epidemiology Study to examine the genetic nature of osteoporosis and its underlying traits, and to identify potential QTLs influencing them. Using quantitative genetics analyses I have identified the extent to which each of the traits measured are influenced by genetic and environmental factors. I further examine the extent to which separate osteoporosis traits are influenced by the same sets of genetic factors, and do the same for these traits in unison with body mass index (BMI), the primary measure of obesity. I also estimate the heritability of osteoporosis traits using actual genetic data rather than traditional assumptions. Finally, by performing a whole-genome linkage analysis I have identified multiple QTLs influencing osteoporosis traits, some of which may act in gender- and age-specific manners. Overall, this work contributes to the existing body of work examining the genetics of osteoporosis. Ultimately, the identification of genes and genetic factors influencing bone traits will aid in the treatment and prevention of osteoporosis and fracture.