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variants (SNVs) associated with neurocognitive impairment (NCI) in perinatally HIV-infected (PHIV) children.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Whole-exome sequencing (WES) was performed on 217 PHIV with cognitive score for age (CSA)\u2005&amp;lt;\u200570 and 247 CSA\u2005\u2265\u200570 (discovery cohort [DC]). SNVs identified in DC were evaluated in 2 validation cohorts (VC). Logistic regression was used to estimate adjusted odds ratios (ORs) for NCI. A human microglia NLRP3 inflammasome assay characterized the role of identified genes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Twenty-nine SNVs in 24 genes reaching P\u2005\u2264\u2005.002 and OR \u2265 1.5 comparing CSA\u2005&amp;lt;\u200570 to CSA \u2265 70 were identified in the DC, of which 3 SNVs were identified in VCs for further study. Combining the 3 cohorts, SNV in CCRL2 (rs3204849) was associated with decreased odds of NCI (P\u2005&amp;lt;\u2005.0001); RETREG1\/FAM134B (rs61733811) and YWHAH (rs73884247) were associated with increased risk of NCI (P\u2005&amp;lt;\u2005.0001 and P\u2005&amp;lt;\u2005.001, respectively). Knockdown of CCRL2 led to decreased microglial release of IL-1\u03b2 following exposure to ssRNA40 while knockdown of RETREG1 and YWHAH resulted in increased IL-1\u03b2 release.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Using WES and 2 VCs, and gene silencing of microglia we identified 3 genetic variants associated with NCI and inflammation in HIV-infected children.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiaa792","type":"journal-article","created":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T20:11:43Z","timestamp":1608667903000},"page":"870-880","source":"Crossref","is-referenced-by-count":9,"title":["Genomics Links Inflammation With Neurocognitive Impairment in Children Living With Human Immunodeficiency Virus Type-1"],"prefix":"10.1093","volume":"224","author":[{"given":"Pratima","family":"Rawat","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of California San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean S","family":"Brummel","sequence":"additional","affiliation":[{"name":"Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumud K","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly A","family":"Frazer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Nichols","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of California San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"George R","family":"Seage","sequence":"additional","affiliation":[{"name":"Harvard T.H. 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