Genome-wide association studies of childhood bone health

Osteoporosis is a major public health concern characterized by low bone mineral density (BMD) and deterioration of bone tissue, causing increased bone fragility and risk of fracture. Though current research has focused primarily on bone health in the elderly, early bone health, including peak BMD attainment, is a strong predictor of bone health later in life. Twin and family studies have demonstrated a strong genetic component in peak BMD, though the specific genes influencing variation in bone development are largely unknown. Moreover, the question of whether the genes influencing bone health during childhood are the same as those influencing bone health later in life is currently unknown. Therefore, to identify variants and genes implicated in childhood bone health, we performed separate genome-wide association studies (GWAS) for ten bone health phenotypes (bone mineral content [BMC] and BMD of the hip, spine, and head, BMC of the whole body, and four measures of hip geometry) in 296 Caucasian children aged 5 years (mean = 5.3) who were enrolled in the Iowa Bone Development Study. Linear regression while adjusting for sex, height, and weight was used to test 548,051 genetic polymorphisms and 7.4 million imputed variants for evidence of association. Genomic regions showing statistical association were scrutinized for relevant gene functions related to bone biology. Five genome- wide significant (P≤5x10-8) and 30 suggestive (P