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Status |
Public on Nov 04, 2021 |
Title |
Identification of known and novel long non-coding RNAs potentially responsible for the effects of BMD GWAS loci |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
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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Overall design |
Acetabular reaming from 17 Boston Medical Center (BMC) patients (ages 43-80 year) undergoing elective hip arthroplasty were collected: 12 Females and 5 Males; 8 Black, 8 White, and 1 Hispanic
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Contributor(s) |
Abood A, Farber C |
Citation missing |
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Submission date |
Nov 01, 2021 |
Last update date |
Nov 06, 2021 |
Contact name |
Abdullah Abood |
E-mail(s) |
aa9gj@virginia.edu
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Phone |
5712744329
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Organization name |
University of Virginia
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Lab |
Farber lab
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Street address |
OMS, Room 3817B
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City |
CHARLOTTESVILLE |
State/province |
VA |
ZIP/Postal code |
22908 |
Country |
USA |
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Platforms (1) |
GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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Samples (17)
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Relations |
BioProject |
PRJNA776822 |
SRA |
SRP344025 |