학술논문
Massively parallel reporter assay confirms regulatory potential of hQTLs and reveals important variants in lupus and other autoimmune diseases.
Document Type
Academic Journal
Author
Fu Y; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.; Kelly JA; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.; Gopalakrishnan J; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA; Neuro-Immune Regulome Unit, National Eye Institute, National Institute of Health, Bethesda, MD 20892, USA.; Pelikan RC; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.; Tessneer KL; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.; Pasula S; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.; Grundahl K; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.; Murphy DA; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.; Gaffney PM; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA. Electronic address: Patrick-Gaffney@omrf.org.
Source
Publisher: Elsevier Inc Country of Publication: United States NLM ID: 101772885 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2666-2477 (Electronic) Linking ISSN: 26662477 NLM ISO Abbreviation: HGG Adv Subsets: MEDLINE
Subject
Language
English
Abstract
We designed a massively parallel reporter assay (MPRA) in an Epstein-Barr virus transformed B cell line to directly characterize the potential for histone post-translational modifications, i.e., histone quantitative trait loci (hQTLs), expression QTLs (eQTLs), and variants on systemic lupus erythematosus (SLE) and autoimmune (AI) disease risk haplotypes to modulate regulatory activity in an allele-dependent manner. Our study demonstrates that hQTLs, as a group, are more likely to modulate regulatory activity in an MPRA compared with other variant classes tested, including a set of eQTLs previously shown to interact with hQTLs and tested AI risk variants. In addition, we nominate 17 variants (including 11 previously unreported) as putative causal variants for SLE and another 14 for various other AI diseases, prioritizing these variants for future functional studies in primary and immortalized B cells. Thus, we uncover important insights into the mechanistic relationships among genotype, epigenetics, and gene expression in SLE and AI disease phenotypes.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)