Genome-Wide Association Analysis of Longitudinal Bone Mineral Content Data From the Iowa Bone Development Study

Abstract

The foundation for osteoporosis risk is, in part, established during childhood, adolescence, and young adulthood, all periods of development when bone mass is acquired rapidly. The relative quantity of bone mass accrued is influenced by both lifestyle and genetic factors, although the genetic component is not yet well understood. The purpose of this study was to use a genome-wide association (GWA) analysis to discover single nucleotide polymorphisms (SNPs) associated with: (1) the sex-specific hip bone mineral content at approximately the age of 19 when the amount of bone accrued is near its peak; and (2) the sex-specific rate of hip bone mineral content accrual during the adolescent growth spurt. The Iowa Bone Development Study, a longitudinal cohort study exploring bone health in children, adolescents, and young adults was the source of data. From this cohort, n = 364 (190 females, 174 males) participants were included in GWA analyses to address (1) and n = 258 participants (125 females and 133 males) were included in GWA analyses to address (2). Twenty SNPS were detected having p < 1.0 × 10−5. Of most biologic relevance were 2 suggestive SNPs (rs2051756 and rs2866908) detected in an intron of the DKK2 gene through the GWA analysis that explored peak bone mass in females.