{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T04:26:01Z","timestamp":1787631961367,"version":"build-2736575974"},"posted":{"date-parts":[[2026,6,10]]},"group-title":"HIV\/AIDS","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["K23GM112526"],"award-info":[{"award-number":["K23GM112526"]}]},{"name":"National Institutes of Health","award":["R01AI143464"],"award-info":[{"award-number":["R01AI143464"]}]},{"name":"National Institutes of Health","award":["U24HG007346"],"award-info":[{"award-number":["U24HG007346"]}]},{"name":"National Institutes of Health","award":["UM1TR004409"],"award-info":[{"award-number":["UM1TR004409"]}]},{"name":"National Institutes of Health","award":["U54AI170792"],"award-info":[{"award-number":["U54AI170792"]}]},{"award":["Y1-AI-5072"],"award-info":[{"award-number":["Y1-AI-5072"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Chan Zuckerberg Biohub San Francisco"},{"award":["HU0001190002"],"award-info":[{"award-number":["HU0001190002"]}],"id":[{"id":"https:\/\/ror.org\/03df8gj37","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,24]]},"abstract":"<jats:p>People with HIV exhibit elevated inflammation and cardiovascular risk despite antiretroviral therapy. To define the genetic architecture of inflammasome-associated inflammation, we performed whole-genome sequencing and quantified plasma IL-6, IL-1\u03b2, and IL-18 in 1,000 ART-suppressed PWH from the U.S. Military HIV Natural History Study. Genome-wide analyses identified 14 loci implicating antiviral defense (DDX17, DDX41, EEA1, BCL11A), lipid metabolism (ABCA1, ABCA12, ABCC1, AGMO), and vascular remodeling (KLHL29, RNF213, ETV1). Transcriptome-wide analyses across cardiovascular and immune tissues identified regulatory programs linking interferon signaling, immune activation, and vascular biology to circulating cytokine levels. Mendelian randomization analyses supported causal relationships between inflammasome-associated cytokines and vascular events. Functional integration with genome-wide CRISPR perturbation datasets in primary CD4\u207a T cells linked cytokine-associated loci to HIV antiviral pathways and cytokine regulatory networks. External validation in cohorts without HIV demonstrated pathway-level convergence despite limited variant-level overlap. These findings define genetic mechanisms linking inflammasome signaling, antiviral defense, and cardiovascular risk.<\/jats:p>","DOI":"10.64898\/2026.06.08.26355202","type":"posted-content","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T17:15:14Z","timestamp":1781111714000},"source":"Crossref","is-referenced-by-count":0,"title":["Host Genetic Regulation of NLRP3 Inflammasome Cytokines Reveals Immune and Vascular Pathways in HIV"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6799-3866","authenticated-orcid":false,"given":"Ryan","family":"Chung","sequence":"first","affiliation":[{"name":"University of California Berkeley, Berkeley, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2204-3562","authenticated-orcid":false,"given":"Namratha Shivani","family":"Chalasani","sequence":"additional","affiliation":[{"name":"University of California San Francisco, San Francisco, 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