MC4R and obesity due to melanocortin 4 receptor deficiency: Moroca et al. found that, compared with CC (MTNR1B) (rs4753426), the risk of AIS significantly increased in Hungarians bearing the CT allele.24 Gary et al. reported lower fracture incidence among elderly Swedish women bearing the MC4R C-allele.124 Curiously, lipocalin 2, a recently identified ligand of MC4R, is secreted by osteoblasts in mice and signals to suppress appetite by binding MC4R-expressing hypothalamic neurons125; MC4R polymorphisms have also been associated with early-onset obesity.126 Mutation of CNR221 and MTNR1B127 had an additional association with human osteoporosis.