Please use this identifier to cite or link to this item:
Title: Expression Quantitative Trait Locus Study of Bone Mineral Density GWAS Variants in Human Osteoclasts.
Authors: Mullin, B. H.
Zhu, K.
Xu, J.
Brown, S. J.
Mullin, S.
Tickner, J.
Pavlos, N. J.
Dudbridge, Frank
Walsh, J. P.
Wilson, S. G.
First Published: 24-Mar-2018
Publisher: American Society for Bone and Mineral Research
Citation: Journal of Bone and Mineral Research, 2018, in press
Abstract: Osteoporosis is a complex disease with a strong genetic component. Genomewide association studies (GWAS) have been very successful at identifying common genetic variants associated with bone parameters. A recently published study documented the results of the largest GWAS for bone mineral density (BMD) performed to date (n = 142,487), identifying 307 conditionally independent single-nucleotide polymorphisms (SNPs) as associated with estimated BMD (eBMD) at the genomewide significance level. The vast majority of these variants are non-coding SNPs. Expression quantitative trait locus (eQTL) studies using disease-specific cell types have increasingly been integrated with the results from GWAS to identify genes through which the observed GWAS associations are likely mediated. We generated a unique human osteoclast-specific eQTL data set using cells differentiated in vitro from 158 participants. We then used this resource to characterize the 307 recently identified BMD GWAS SNPs for association with nearby genes (±500 kb). After correction for multiple testing, 24 variants were found to be significantly associated with the expression of 32 genes in the osteoclast-like cells. Bioinformatics analysis suggested that these variants and those in strong linkage disequilibrium with them are enriched in regulatory regions. Several of the eQTL associations identified are relevant to genes that present strongly as having a role in bone, particularly IQGAP1, CYP19A1, CTNNB1, and COL6A3. Supporting evidence for many of the associations was obtained from publicly available eQTL data sets. We have also generated strong evidence for the presence of a regulatory region on chromosome 15q21.2 relevant to both the GLDN and CYP19A1 genes. In conclusion, we have generated a unique osteoclast-specific eQTL resource and have used this to identify 32 eQTL associations for recently identified BMD GWAS loci, which should inform functional studies of osteoclast biology.
DOI Link: 10.1002/jbmr.3412
ISSN: 0884-0431
eISSN: 1523-4681
Embargo on file until: 24-Mar-2019
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2018, American Society for Bone and Mineral Research. Deposited with reference to the publisher’s open access archiving policy. (
Description: The file associated with this record is under embargo until 12 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.
Appears in Collections:Published Articles, Dept. of Health Sciences

Files in This Item:
File Description SizeFormat 
OC eQTL manuscript - eBMD variants - JBMR format_revised 160218.docxPost-review (final submitted author manuscript)175.77 kBUnknownView/Open
OC+eQTL+manuscript+-+eBMD+variants+-+JBMR+format_revised+160218.pdfPost-review (final submitted author manuscript)429.87 kBAdobe PDFView/Open

Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.