Two Populations-Based Pharmacogenomics Investigation in Osteoporosis Susceptibility and Raloxifene Treatment Efficacy – across Taiwanese and Japanese

Osteoporosis is among the most common and costly diseases and is increasing in prevalence owing to the ageing of our global population. Clinically defined largely through bone mineral density, osteoporosis and osteoporotic fractures have reasonably high heritability, prompting much effort to identify the genetic determinants of this disease. Recently, several groups conducted genome-wide association studies and identified many loci associated with susceptibility to osteoporosis mainly in Caucasian; however, the genetic contribution to osteoporosis is not entirely known. To uncover additional susceptibility gene(s) for osteoporosis, we will perform a genome wide association study in a Taiwanese population. In this study, we recruit subjects who fulfill inclusion criteria in the Taipei Medical University Hospital and Wan-Feng Hospital. We select 94 patients with drug treatment to conduct genome wide association study. Our current study already revealed several candidate loci associated with bone mineral density. Therefore, we will further use 500 subject’s GWAS data from Taiwan Biobank to validate our results. We will further use target sequencing to refine to causal variant of low bone mineral density. Besides, we will collaborate with Prof. Mushiroda of RIKEN to investigate the possible genetic variant cause poor response to raloxifene. By recognizing candidate genes and pathway, we will be able to predict drug to treat these poor response patients. The results may be applied to preventive medicine and intervention to reduce the risk of osteoporosis in a Taiwanese population. Moreover, the drug reposition provide a new insight to osteoporosis drug development.