Genetics of pleiotropic effects of dexamethasone

Objectives Glucocorticoids such as dexamethasone have pleiotropic effects, including desired antileukemic, anti-inflammatory or immunosuppressive effects, and undesired metabolic or toxic effects. The most serious adverse effects of dexamethasone among patients with acute lymphoblastic leukemia (ALL) are osteonecrosis and thrombosis. To identify inherited genomic variation involved in these serious adverse effects, we performed genome-wide association studies (GWAS) by analyzing 14 pleiotropic glucocorticoid phenotypes in 391 patients with ALL.