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/

Zendy Open

Presents the pdf analysis as premium feature

PDF Analysis

Insights

Presents the summarisation as premium feature

Summarisation

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Background:  Bone mineral density (BMD) is a heritable phenotype that predictsfracture risk. We performed fine-mapping by targeted sequencing at  WLS, MEF2C,ARHGAP1/F2  and  JAG1  loci prioritized by eQTL and bioinformaticapproaches among 56 BMD loci from our previous GWAS meta-analysis.  Methods andResults:  Targeted sequencing was conducted in 1,291 Caucasians from theFramingham Heart Study ( n =  925) and Cardiovascular Health Study( n =  366), including 206 women and men with extreme low femoral neck(FN) BMD. A total of 4,964 sequence variants (SNVs) were observed and 80% were rare withMAF &lt;1%. The associations between previously identified SNPs in these loci and BMD,while nominally significant in sequenced participants, were no longer significant aftermultiple testing corrections. Conditional analyses did not find protein-coding variantsthat may be responsible for GWAS signals. On the other hand, in the sequenced subjects, weidentified novel associations in  WLS ,  ARHGAP1 , and5’ of MEF2C( P- values &lt; 8x10  −   5 ; false discovery rate(FDR) q-values &lt; 0.01) that were much more strongly associated with BMD compared to theGWAS SNPs. These associated SNVs are less-common; independent from previous GWAS signalsin the same loci; and located in gene regulatory elements.  Conclusions:  Ourfindings suggest that protein-coding variants in selected GWAS loci did not contribute toGWAS signals. By performing targeted sequencing in GWAS loci, we identified less-commonand rare non-coding SNVs associated with BMD independently from GWAS common SNPs,suggesting both common and less-common variants may associate with disease risks andphenotypes in the same loci.

human molecular genetics

Targeted sequencing of genome wide significant loci associated with bone           mineral density (BMD) reveals significant novel and rare variants: the Cohorts for Heart           and Aging Research in Genomic Epidemiology (CHARGE) targeted sequencing           study