Javier Botey-Bataller, Nienke van Unen, Marc Blaauw, Willem A. J. W. Vos, Louise van Eekeren, Nadira Vadaq, Vasiliki Matzaraki, Annelies Verbon, Albert L. Groenendijk, Jéssica C. dos Santos, Maartje C. P. Cleophas, Janneke E. Stalenhoef, Marvin A. H. Berrevoets, Xun Jiang, Manoj K. Gupta, Nhan Nguyen, Cheng-Jian Xu, Leo A. B. Joosten, Mihai G. Netea, André J. A. M. van der Ven, Yang Li
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Genetic and molecular landscape of comorbidities in people living with HIV
People living with HIV (PLHIV) have an increased susceptibility to non-AIDS comorbidities. In this study, we systematically profiled 1,342 PLHIV across five omics layers and immune function. We found latent factors, resulting from integrating epigenomics, transcriptomics, proteomics, metabolomics and immune responses, linked to cardiovascular diseases, the presence of carotid plaque and chronic obstructive pulmonary disease in PLHIV. Mapping four omics layers to genetic variation identified 5,962 molecular quantitative trait loci, illustrating a common genetic regulation in PLHIV compared to healthy individuals. By performing Mendelian randomization, we uncovered host genetic-driven changes in baseline molecules causally related to immune responses upon stimulation with inactivated pathogens. Lastly, we uncovered that the inflammasome, genetically regulated by the NLRP12 locus, contributes to systemic inflammation across multiple molecular layers. This study offers a unique catalog of genetic and molecular determinants of immune function in PLHIV and elucidates molecular pathways driving inter-individual variation in immune response and comorbidities.
期刊介绍：
Nature Medicine is a monthly journal publishing original peer-reviewed research in all areas of medicine. The publication focuses on originality, timeliness, interdisciplinary interest, and the impact on improving human health. In addition to research articles, Nature Medicine also publishes commissioned content such as News, Reviews, and Perspectives. This content aims to provide context for the latest advances in translational and clinical research, reaching a wide audience of M.D. and Ph.D. readers. All editorial decisions for the journal are made by a team of full-time professional editors.
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Nature Medicine is also committed to facilitating communication between translational and clinical researchers. As such, we consider “hybrid” studies with preclinical and translational findings reported alongside data from clinical studies.
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