Multiple Functional Variants at 13q14 Risk Locus for Osteoporosis Regulate RANKL Expression Through Long‐Range Super‐Enhancer

ABSTRACT RANKL is a key regulator involved in bone metabolism, and a drug target for osteoporosis. The clinical diagnosis and assessment of osteoporosis are mainly based on bone mineral density (BMD). Previous powerful genomewide association studies (GWASs) have identified multiple intergenic single...

Full description

Saved in:
Bibliographic Details
Published in:Journal of bone and mineral research 2018-07, Vol.33 (7), p.1335-1346
Main Authors: Zhu, Dong‐Li, Chen, Xiao‐Feng, Hu, Wei‐Xin, Dong, Shan‐Shan, Lu, Bing‐Jie, Rong, Yu, Chen, Yi‐Xiao, Chen, Hao, Thynn, Hlaing Nwe, Wang, Nai‐Ning, Guo, Yan, Yang, Tie‐Lin
Format: Article
Language:English
Subjects:
Bioinformatics
Bone mineral density
Bone turnover
Chromatin
Chromosome 13
CRISPR
CRISPR/CAS9
Data processing
Drug metabolism
Epigenetics
Gene expression
Genome editing
Genomes
Localization
LONG‐RANGE
OSTEOPOROSIS
Precision medicine
Quantitative trait loci
RANKL
Single-nucleotide polymorphism
SUPER‐ENHANCER
Therapeutic applications
TRANCE protein
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:ABSTRACT RANKL is a key regulator involved in bone metabolism, and a drug target for osteoporosis. The clinical diagnosis and assessment of osteoporosis are mainly based on bone mineral density (BMD). Previous powerful genomewide association studies (GWASs) have identified multiple intergenic single‐nucleotide polymorphisms (SNPs) located over 100 kb upstream of RANKL and 65 kb downstream of AKAP11 at 13q14.11 for osteoporosis. Whether these SNPs exert their roles on osteoporosis through RANKL is unknown. In this study, we conducted integrative analyses combining expression quantitative trait locus (eQTL), genomic chromatin interaction (high‐throughput chromosome conformation capture [Hi‐C]), epigenetic annotation, and a series of functional assays. The eQTL analysis identified six potential functional SNPs (rs9533090, rs9594738, r8001611, rs9533094, rs9533095, and rs9594759) exclusively correlated with RANKL gene expression (p 
ISSN:0884-0431
1523-4681
DOI:10.1002/jbmr.3419