{"doi":"10.1002/jbmr.4622","title":"Identification of Known and Novel Long Noncoding RNAs Potentially Responsible for the Effects of Bone Mineral Density (BMD) Genomewide Association Study (GWAS) Loci","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 noncoding 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 single-nucleotide polymorphisms (SNPs) demonstrating AI. Using GTEx data we identified an additional 31 lncRNAs whose expression was associated (false discovery rate [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. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).","journal":"Journal of Bone and Mineral Research","year":2020,"id":74541,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9469,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":391458,"name":"Larry D. Mesner","orcid":null,"position":1,"is_corresponding":false},{"id":390119,"name":"Will Rosenow","orcid":"0000-0002-0359-8410","position":2,"is_corresponding":false},{"id":390120,"name":"Basel M. Al‐Barghouthi","orcid":"0000-0001-9816-8044","position":3,"is_corresponding":false},{"id":390121,"name":"Nina B. Horowitz","orcid":"0000-0002-5151-7945","position":4,"is_corresponding":false},{"id":390122,"name":"Elise F. Morgan","orcid":"0000-0002-3994-1890","position":5,"is_corresponding":false},{"id":391459,"name":"Louis C. Gerstenfeld","orcid":null,"position":6,"is_corresponding":false},{"id":24960,"name":"Charles R. Farber","orcid":"0000-0002-6748-4711","position":7,"is_corresponding":false},{"id":390118,"name":"Abdullah Abood","orcid":"0000-0001-5714-6375","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-18T21:46:11.663457Z","pmid":"35695880","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}