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

• DOI: 10.1038/s41467-019-09302-x
• Publication Date: 2019-04-18T14:59:24Z
• Authors: 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
• Keywords: Genome-wide Association Study; Candidate gene

Abstract Osteoporosis is a devastating disease with an essential genetic component. GWAS have discovered signals robustly associated 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 massively parallel, high resolution Capture C based method order simultaneously characterize genome-wide interactions all promoters. By intersecting our ATAC-seq data, observe consistent contacts between candidate causal variants putative target promoters open chromatin for ~ 17% 273 BMD loci investigated. Knockdown two novel implicated genes, ING3 at ‘ CPED1-WNT16 ’ EPDR1 STARD3NL ’, inhibits osteoblastogenesis, while promoting adipogenesis. This approach therefore aids discovery osteoporosis, here on example relevant genes involved fate determination progenitors, can be applied other common diseases.