Insomnia is the second most prevalent mental disorder, with no sufficient treatment available. Despite substantial heritability, insight into the associated genes and neurobiological pathways remains limited. Here, we use a large genetic association sample (n = 1,331,010) to detect novel loci and gain insight into the pathways, tissue and cell types involved in insomnia complaints. We identify 202 loci implicating 956 genes through positional, expression quantitative trait loci, and chromatin mapping. The meta-analysis explained 2.6% of the variance. We show gene set enrichments for the axonal part of neurons, cortical and subcortical tissues, and specific cell types, including striatal, hypothalamic, and claustrum neurons. We found considerable genetic correlations with psychiatric traits and sleep duration, and modest correlations with other sleep-related traits. Mendelian randomization identified the causal effects of insomnia on depression, diabetes, and cardiovascular disease, and the protective effects of educational attainment and intracranial volume. Our findings highlight key brain areas and cell types implicated in insomnia, and provide new treatment targets.
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Drugs Aging
January 2025
Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
IgG4-related disease (IgG4-RD) is an immune-mediated disorder characterized by organ enlargement and dysfunction. The formation of tertiary lymphoid tissues (TLTs) in affected organs is crucial for understanding IgG4-RD, as T follicular helper (Tfh) 2 cells within TLTs drive IgG4+B cell differentiation, contributing to mass formation. Key cytokines IL-4 and IL-10, produced by Tfh2 cells, are essential for this process.
View Article and Find Full Text PDFDiscov Oncol
January 2025
Department of General Surgery, The Second Affiliated Hospital of the Air Force Medical University, Xi'an, 710038, China.
A common digestive system cancer with a dismal prognosis and a high death rate globally is breast cancer (BRCA). BRCA recurrence, metastasis, and medication resistance are all significantly impacted by cancer stem cells (CSCs). However, the relationship between CSCs and the tumor microenvironment in BRCA individuals remains unknown, and this information is critically needed.
View Article and Find Full Text PDFClin Exp Med
January 2025
Universitat Autònoma de Barcelona, Bellaterra, Spain.
Alcohol-related cirrhosis (AC) is a condition that impacts in immunity. We analyzed changes over time in CD4subsets in AC-patients. We included patients with alcohol use disorder admitted at least twice for treatment.
View Article and Find Full Text PDFCytotherapy
December 2024
Department of Medicine, Kuopio University Hospital, Kuopio, Finland. Electronic address:
The amount of CD34 cells has been for decades the most important marker of autologous graft quality, but other graft cells, including various lymphocyte subsets, have gained some interest. This review attempts to summarize what is known about autograft cellular composition regarding post-transplant outcomes. The amount of CD34 cells in the graft is associated with tempo of platelet recovery.
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November 2024
Institute of Immunology and Immunotherapy, College of Medicine and Health, University of Birmingham, Birmingham, UK. Electronic address:
Background Aims: Extracellular vesicles (EVs) have gained traction as potential cell-free therapeutic candidates. Development of purification methods that are scalable and robust is a major focus of EV research. Yet there is still little in the literature that evaluates purification methods against potency of the EV product.
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