{"doi":"10.1093/infdis/jiaa792","title":"Genomics Links Inflammation With Neurocognitive Impairment in Children Living With Human Immunodeficiency Virus Type-1","abstract":"BACKGROUND: We identified host single-nucleotide variants (SNVs) associated with neurocognitive impairment (NCI) in perinatally HIV-infected (PHIV) children. METHODS: Whole-exome sequencing (WES) was performed on 217 PHIV with cognitive score for age (CSA) < 70 and 247 CSA ≥ 70 (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. RESULTS: Twenty-nine SNVs in 24 genes reaching P ≤ .002 and OR ≥ 1.5 comparing CSA < 70 to CSA ≥ 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 < .0001); RETREG1/FAM134B (rs61733811) and YWHAH (rs73884247) were associated with increased risk of NCI (P < .0001 and P < .001, respectively). Knockdown of CCRL2 led to decreased microglial release of IL-1β following exposure to ssRNA40 while knockdown of RETREG1 and YWHAH resulted in increased IL-1β release. CONCLUSIONS: Using WES and 2 VCs, and gene silencing of microglia we identified 3 genetic variants associated with NCI and inflammation in HIV-infected children.","journal":"The Journal of Infectious Diseases","year":2020,"id":85115,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.6626,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":435842,"name":"Sean S. Brummel","orcid":"0000-0002-4116-404X","position":1,"is_corresponding":false},{"id":436857,"name":"Kumud K. Singh","orcid":null,"position":2,"is_corresponding":false},{"id":13662,"name":"Jihoon Kim","orcid":"0000-0002-5351-238X","position":3,"is_corresponding":false},{"id":95977,"name":"Kelly A. Frazer","orcid":"0000-0002-6060-8902","position":4,"is_corresponding":false},{"id":435843,"name":"Sharon Nichols","orcid":"0000-0002-2838-8268","position":5,"is_corresponding":false},{"id":382517,"name":"George R. Seage","orcid":"0000-0001-5657-2970","position":6,"is_corresponding":false},{"id":368526,"name":"Paige L. Williams","orcid":"0000-0002-7160-574X","position":7,"is_corresponding":false},{"id":436858,"name":"Russell B. Van Dyke","orcid":null,"position":8,"is_corresponding":false},{"id":13530,"name":"Olivier Harismendy","orcid":"0000-0002-8098-9888","position":9,"is_corresponding":false},{"id":436859,"name":"Rodney Trout","orcid":null,"position":10,"is_corresponding":false},{"id":69476,"name":"Stephen A. Spector","orcid":"0000-0002-1882-4855","position":11,"is_corresponding":false},{"id":435841,"name":"Pratima Rawat","orcid":"0000-0002-4552-5156","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-18T21:56:02.794896Z","pmid":"33373444","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}