English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  Genome-wide association studies (GWASs) routinely identify loci associated with risk factors for osteoporosis. However, GWASs with relatively small sample sizes still lack sufficient power to ascertain the majority of genetic variants with small to modest effect size, which may together truly influence the phenotype. The loci identified only account for a small percentage of the heritability of osteoporosis. This study aims to identify novel genetic loci associated with DXA-derived femoral neck (FNK) bone mineral density (BMD) and quantitative ultrasound of the heel calcaneus estimated BMD (eBMD), and to detect shared/causal variants for the two traits, to assess whether the SNPs or putative causal SNPs associated with eBMD were also associated with FNK-BMD.    Methods  Novel loci associated with eBMD and FNK-BMD were identified by the genetic pleiotropic conditional false discovery rate (cFDR) method. Shared putative causal variants between eBMD and FNK-BMD and putative causal SNPs for each trait were identified by the colocalization method. Mendelian randomization analysis addresses the causal relationship between eBMD/FNK-BMD and fracture.    Results  We identified 9,500 (cFDR < 9.8E-6), 137 (cFDR < 8.9E-4) and 124 SNPs associated with eBMD, FNK-BMD, and both eBMD and FNK-BMD, respectively, with 37 genomic regions where there was a SNP that influences both eBMD and FNK-BMD. Most genomic regions only contained putative causal SNPs associated with eBMD and 3 regions contained two distinct putative causal SNPs influenced both traits, respectively. We demonstrated a causal effect of FNK-BMD/eBMD on fracture.    Conclusion  Most of SNPs or putative causal SNPs associated with FNK-BMD were also associated with eBMD. However, most of SNPs or putative causal SNPs associated with eBMD were not associated with FNK-BMD. The novel variants we identified may help to account for the additional proportion of variance of each trait and advance our understanding of the genetic mechanisms underlying osteoporotic fracture.

Identifying Pleiotropic SNPs Associated With Femoral Neck and Heel Bone Mineral Density