Multiple gene polymorphisms can improve prediction of nonvertebral fracture in postmenopausal women

ABSTRACT Clinical risk factors (CRFs), with or without bone mineral density (BMD), are used to determine the risk of osteoporotic fracture (OF), which has a heritable component. In this study we investigated whether genetic profiling can additionally improve the ability to predict OF. Using 1229 unrelated Korean postmenopausal women, 39 single‐nucleotide polymorphisms (SNPs) in 30 human genomic loci were tested for association with osteoporosis‐related traits, such as BMD, osteoporosis, vertebral fracture (VF), nonvertebral fracture (NVF), and any fracture. To estimate the effects of genetic profiling, the genetic risk score (GRS) was calculated using five prediction models: (Model I) GRSs only; (Model II) BMD only; (Model III) CRFs only; (Model IV) CRFs and BMD; and (Model V) CRFs, BMD, and GRS. A total of 21 SNPs within 19 genes associated with one or more osteoporosis‐related traits and were included for GRS calculation. GRS associated with BMD before and after adjustment for CRFs (p ranging from