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Background: Although genome-wide association studies (GWAS) have identified over 100 genetic loci associated with rheumatoid arthritis (RA), our ability to translate these results into disease understanding and novel therapeutics is limited. Most RA GWAS loci reside outside of protein-coding regions and likely affect distal transcriptional enhancers. Furthermore, GWAS do not identify the cell types where the associated causal gene functions. Thus, mapping the transcriptional regulatory roles of GWAS hits and the relevant cell types will lead to better understanding of RA pathogenesis.
Results: We combine the whole-genome sequences and blood transcription profiles of 377 RA patients and identify over 6000 unique genes with expression quantitative trait loci (eQTLs). We demonstrate the quality of the identified eQTLs through comparison to non-RA individuals. We integrate the eQTLs with immune cell epigenome maps, RA GWAS risk loci, and adjustment for linkage disequilibrium to propose target genes of immune cell enhancers that overlap RA risk loci. We examine 20 immune cell epigenomes and perform a focused analysis on primary monocytes, B cells, and T cells.
Conclusions: We highlight cell-specific gene associations with relevance to RA pathogenesis including the identification of FCGR2B in B cells as possessing both intragenic and enhancer regulatory GWAS hits. We show that our RA patient cohort derived eQTL network is more informative for studying RA than that from a healthy cohort. While not experimentally validated here, the reported eQTLs and cell type-specific RA risk associations can prioritize future experiments with the goal of elucidating the regulatory mechanisms behind genetic risk associations.
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http://dx.doi.org/10.1186/s13059-016-0948-6 | DOI Listing |
Cell Mol Biol Lett
December 2024
Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, 178 East Ganjiang Road, Suzhou, 215000, China.
Gastric cancer (GC) represents a prevalent malignancy globally, often diagnosed at advanced stages owing to subtle early symptoms, resulting in a poor prognosis. Exosomes are extracellular nano-sized vesicles and are secreted by various cells. Mounting evidence indicates that exosomes contain a wide range of molecules, such as DNA, RNA, lipids, and proteins, and play crucial roles in multiple cancers including GC.
View Article and Find Full Text PDFBMC Complement Med Ther
December 2024
School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Background: Amphetamine-type stimulant (ATS) abuse is strongly associated with an elevated risk of HIV infection and transmission. Antiretroviral therapy (ART) serves as the primary approach for managing HIV infection and AIDS progression. However, ATS abuse diminishes the efficacy of ART in HIV/AIDS patients, amplifying the vulnerability to immunological non-response (INR) and ultimately increasing the incidence rate and mortality of opportunistic infections.
View Article and Find Full Text PDFBackground: Periodontitis is among the most prevalent inflammatory conditions and greatly impacts oral health. This study aimed to elucidate the role of basement membrane-related genes in the pathogenesis and diagnosis of periodontitis.
Methods: GSE10334 was used for identification of hub genes via the differential analysis, protein-protein interaction network, MCC and DMNC algorithms, and evaluation via LASSO regression and support vector machine analysis to identify basement membrane-related markers in patients with periodontitis.
BMC Cancer
December 2024
Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150000, China.
Background: The therapeutic efficacy and prognosis of various tumors can be assessed using the systemic immune-inflammatory index (SII) and prognostic nutritional index (PNI). Despite their potential, no studies have investigated the prognostic value of the combined SII-PNI score for outcomes in patients with extensive small cell lung cancer (ES-SCLC) treated with chemotherapy and immune checkpoint inhibitors (ICIs).
Materials And Methods: Our study retrospectively examined 213 ES-SCLC patients treated with chemotherapy and ICIs across two institutions.
Mol Med
December 2024
Department of Neurobiology and Anatomy, Key Laboratory of Neurobiology, Xuzhou Medical University, 209, Tongshan Road, Xuzhou, 221004, China.
Doublecortin (DCX) is a microtubule-associated protein known to be a key regulator of neuronal migration and differentiation during brain development. However, the role of DCX, particularly in regulating the survival and growth of glioma cells, remains unclear. In this study, we utilized CRISPR/Cas9 technology to knock down DCX in the human glioma cell line (U251).
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!