Identification of known and novel long non-coding RNAs potentially responsible for the effects of BMD GWAS loci
Files
First author draft
Date
2021
Authors
Abood, Abdullah
Mesner, Larry
Rosenow, Will
Al-Barghouthi, Basel M.
Horwitz, Nina
Morgan, Elise F.
Gerstenfeld, Louis C.
Farber, Charles R.
Version
First author draft
OA Version
Citation
A. Abood, L. Mesner, W. Rosenow, B.M. Al-Barghouthi, N. Horwitz, E.F. Morgan, L.C. Gerstenfeld, C.R. Farber. "Identification of known and novel long non-coding RNAs potentially responsible for the effects of BMD GWAS loci." https://doi.org/10.1101/2021.11.04.467171
Abstract
Osteoporosis, characterized by low bone mineral density (BMD), is the most common complex disease affecting bone and constitutes a major societal health problem. Genome-wide association studies (GWASs) have identified over 1100 associations influencing BMD. It has been shown that perturbations to long non-coding RNAs (lncRNAs) influence BMD and the activities of bone cells; however, the extent to which lncRNAs are involved in the genetic regulation of BMD is unknown. Here, we combined the analysis of allelic imbalance (AI) in human acetabular bone fragments with a transcriptome-wide association study (TWAS) and expression quantitative trait loci (eQTL) colocalization analysis using data from the Genotype-Tissue Expression (GTEx) project to identify lncRNAs potentially responsible for GWAS associations. We identified 27 lncRNAs in bone that are located in proximity to a BMD GWAS association and harbor SNPs demonstrating AI. Using GTEx data we identified an additional 31 lncRNAs whose expression was associated (FDR correction<0.05) with BMD through TWAS and had a colocalizing eQTL (regional colocalization probability (RCP)>0.1). The 58 lncRNAs are located in 43 BMD associations. To further support a causal role for the identified lncRNAs, we show that 23 of the 58 lncRNAs are differentially expressed as a function of osteoblast differentiation. Our approach identifies lncRNAs that are potentially responsible for BMD GWAS associations and suggest that lncRNAs play a role in the genetics of osteoporosis.
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