The cannabinoid receptor type 2 (CNR2) gene is associated with human osteoporosis

Genetic variants within the CNR2 gene encoding the cannabinoid receptor CB2 have been shown to be associated with osteoporosis and low bone mineral density (BMD) in case-control studies. We now examined the association of polymorphisms in CNR2 with hand bone strength in an ethnically homogeneous healthy family sample of European origin (Chuvashians) living in Russia. We show that non-synonymous CNR2 SNPs are signiWcantly associated with radiographic hand BMD and breaking bending resistance index (BBRI) by two diVerent transmission disequilibrium tests. For both tests highly signiWcant p values (ranging from 0.007 to 0.008 for hand BMD, and from 0.001 to 0.003 for BBRI) were also obtained with additional SNPs at the CNR2 locus. The associations remained signiWcant after correction for multiple testing. In conclusion, in addition to the association of CNR2 polymorphisms with low BMD at selected clinically relevant skeletal sites, we now report their signiWcant association with hand bone strength phenotypes using a family-based study design implying an even broader impact of genetic variation at the CNR2 locus on bone structure and function.