Pulse Brain · Growing Health Evidence Index
Peer-reviewed

Genome-scale Capture C promoter interactions implicate effector genes at GWAS loci for bone mineral density

Alessandra Chesi, Yadav Wagley, Matthew E. Johnson, Elisabetta Manduchi, Chun Su, Sumei Lu, Michelle E. Leonard, Kenyaita M. Hodge, James A. Pippin, Kurt D. Hankenson, Andrew D. Wells, Struan F.A. Grant

Nature Communications · 2019

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Summary

Osteoporosis is a devastating disease with an essential genetic component. GWAS have discovered genetic signals robustly associated with bone mineral density (BMD), but not the precise localization of effector genes. Here, we carry out physical and direct variant to gene mapping in human mesenchymal progenitor cell-derived osteoblasts employing a massively parallel, high resolution Capture C based method in order to simultaneously characterize the genome-wide interactions of all human promoters. By intersecting our Capture C and ATAC-seq data, we observe consistent contacts between candidate causal variants and putative target gene promoters in open chromatin for ~ 17% of the 273 BMD loci investigated. Knockdown of two novel implicated genes, ING3 at 'CPED1-WNT16' and EPDR1 at 'STARD3NL',

Subject
Other / interdisciplinary
Source type
Peer-reviewed study
System type
Other
DOI
10.1038/s41467-019-09302-x
Catalogue ID
SNmp99jcen-20k43j
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