In the current study, rs7623768 in CRTAP is significantly associa

In the current study, rs7623768 in CRTAP is significantly associated with femoral neck BMD (p = 0.009), and the haplotype G–C of rs4076086–rs7623768 is consistently associated with femoral neck BMD (p = 0.003) Epacadostat in vivo and total hip BMD (p = 0.007). We recently demonstrated that variants of the sclerostin gene that cause sclerosteosis and van Buchem disease are also associated with osteoporosis [54]. Association of CRTAP polymorphisms with femoral neck BMD further supports previous observations that genes associated with monogenic bone diseases also contribute to BMD variation and osteoporosis risk in the general population. PTHR1 is a member of the superfamily of G-protein-coupled receptors.

The gain-of-function mutations in the PTHR1 gene cause Jansen’s metaphyseal chondrodysplasia that is characterized by growth plate abnormalities and increased bone resorption, while loss-of-function

mutations in PTHR1 cause selleck screening library Blomstrand chondrodysplasia which is characterized by advanced endochondral bone maturation and increased BMD. In the current study, PTHR1 showed haplotypic association with lumbar spine and femoral neck BMD (p = 0.02 and p = 0.044, respectively), although no association was observed between BMD and individual SNP in PTHR1. It is worth noting that two previous studies also reported the association of BMD with haplotypes but not single SNPs in this region of PTHR1 [29, 31]. It is likely that untyped Emricasan cell line common variant or multiple rare variants are responsible for the observed association. Because SNPs in this region of

PTHR1 are in strong LD, it is difficult to clearly define the primary associated variant(s) by population genetics approaches. PRKD3 Functional assessment of the variants via computational methods, laboratory assays, or model systems will be required to determine variant(s) responsible and the mechanism of the observed association. The strength of our study is that the selected sampling strategy can substantially increase power over random sampling for detection of allelic association [55]. Assuming a marker is in complete LD (D′ = 1) with a QTL or the causal allele accounting for 1% of BMD variation and the MAFs of the marker and QTL are both 0.1, more than 98% power can be achieved to detect the additive genetic effects of the marker at a significance level of α = 0.05 in the whole study population. Making the same assumptions with use of the same parameters, the power was 87%, 77%, and 73% for lumbar spine, femoral neck, and total hip BMD, respectively, in the postmenopausal women subgroup. Based on the power calculation, our study should have sufficient power to detect any association between a marker and BMD. Nonetheless, this study failed to replicate the association between rs7646054 in ARFGEH3 and BMD in postmenopausal women recently observed by Mullin et al. [14].

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