{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"contact_person":["Luisa Pereira"],"full_dataset_link":["https://ega-archive.org/dacs/EGAC00001000601"],"host":["EGA"],"description":["EGA DAC EGAC00001000601"],"repository":["EGA"],"email":["lpereira@ipatimup.pt"],"pubmed_abstract":["Ethnic groups can display differential genetic susceptibility to infectious diseases. The arthropod-born viral dengue disease is one such disease, with empirical and limited genetic evidence showing that African ancestry may be protective against the haemorrhagic phenotype. Global ancestry analysis based on high-throughput genotyping in admixed populations can be used to test this hypothesis, while admixture mapping can map candidate protective genes. A Cuban dengue fever cohort was genotyped using a 2.5 million SNP chip. Global ancestry was ascertained through ADMIXTURE and used in a fine-matched corrected association study, while local ancestry was inferred by the RFMix algorithm. The expression of candidate genes was evaluated by RT-PCR in a Cuban dengue patient cohort and gene set enrichment analysis was performed in a Thai dengue transcriptome. OSBPL10 and RXRA candidate genes were identified, with most significant SNPs placed in inferred weak enhancers, promoters and lncRNAs. OSBPL10 had significantly lower expression in Africans than Europeans, while for RXRA several SNPs may differentially regulate its transcription between Africans and Europeans. Their expression was confirmed to change through dengue disease progression in Cuban patients and to vary with disease severity in a Thai transcriptome dataset. These genes interact in the LXR/RXR activation pathway that integrates lipid metabolism and immune functions, being a key player in dengue virus entrance into cells, its replication therein and in cytokine production. Knockdown of OSBPL10 expression in THP-1 cells by two shRNAs followed by DENV2 infection tests led to a significant reduction in DENV replication, being a direct functional proof that the lower OSBPL10 expression profile in Africans protects this ancestry against dengue disease."],"pubmed_title":["OSBPL10, RXRA and lipid metabolism confer African-ancestry protection against dengue haemorrhagic fever in admixed Cubans."],"pubmed_authors":["Sierra Beatriz B, Triska Petr P, Soares Pedro P, Garcia Gissel G, Perez Ana B AB, Aguirre Eglys E, Oliveira Marisa M, Cavadas Bruno B, Regnault Béatrice B, Alvarez Mayling M, Ruiz Didye D, Samuels David C DC, Sakuntabhai Anavaj A, Pereira Luisa L, Guzman Maria G MG"],"pubmed_title_synonyms":["RXRalpha1, Hemorrhagic Dengue, Hemorrhagic Fever, Nr2b1, 9530071D11Rik, DHF, Dengue hemorrhagic fever, Dengue, OPR-10, lipid metabolism, C820004B04Rik, Thai Hemorrhagic Fever, NR2B1, Metabolism, Lipid, Singapore Hemorrhagic Fever., ORP10, OSBP9, African unspecified, Philippine Hemorrhagic Fever, Dengue Shock Syndrome, Dengue haemorrhagic fever, 4933433D06Rik"],"name_synonyms":["classical dengue, hemorrhagic dengue, Thai hemorrhagic fever, Singapore hemorrhagic fever., Philippine hemorrhagic fever"],"pubmed_abstract_synonyms":["RLD1, Classical Dengues, LXRbeta, IPP2A2, Materials, ecdysteroid hormone receptor activity, predisposition, determination, methionine aminopeptidase activity, Gene Expression Profile, Infestations and Infections, RT-PCR, Break-Bone Fever, Profiles, CG30327, 5730420M11Rik, CG11478, diseases, Associations, Break Bone Fever, Virus, 1, 2, NER1, Ethnic Group, diseases and disorders, cytokine secretion, hemorrhagic dengue, Infectious Diseases, Singapore hemorrhagic fever., 2310040B03Rik, peptidase M activity, 4933433D06Rik, adenomas, rabGAPLP, DmelCG42257, SET, human disease, L-methionine aminopeptidase activity, LXR, glucocorticoid receptor activity, calcitriol receptor activity, Genetic Predisposition, TAF-I, Chip, ChIP, Unr1, Unr2, CHIP, Genetic Susceptibilities, RabGAP-5, Signatures, genetic predispositions, genetic, DmelCG4299, Fever Viruses, chip, IGAAD, set, DmelCG10574, Expression Signature, C820004B04Rik, RUSC3, interleukin secretion, Fever, AW046544, Transcriptomes, Homo sapiens disease, retinoic acid receptor activity, Infections and Infestations, RIP15, transcription from bacterial-type RNA polymerase promoter, Breakbone, phapii, thyroid hormone receptor activity, l(2)k04405, Infectious Disease, Data Set, Communicable Diseases, Expression Profiles, familial, MYH-associated polyposis, autosomal recessive familial adenomatous polyposis, Maps, StF-IT-1, retinoid-X receptor activity, AU018371, 9-cis retinoic acid receptor activity, interferon production, UR, LXRB, Communicable Disease, Gene Expression, Dengue fever, interleukin production, CG6393, Algorithm, Expression Signatures, Lipid, Diseases, Genetic Materials, 25-(OH)2D3 receptor activity, Expression Profile, Philippine hemorrhagic fever, Genetic Material, activation, autosomal recessive, Break-Bone, SDCCAG7, Transcriptome Profiles, RUTBC3, Dmel_CG6393, Thai hemorrhagic fever, dLdb, HLA-DR-associated protein II, DI-2, Communicable, RXR, Breakbone Fever Viruses, I-2Dm, Fever Virus, AI194859, Nationalities, Breakbone Fever, Infection and Infestation, INSDC_feature:gene, Predisposition, CG4299, Unr, estrogen nuclear receptor activity, RABGAP5, juvenile hormone receptor activity, I-2PP1, RXRalpha1, Cell Line, Phenotypes, OR-1, disease, ligand-dependent transcription factor activity, TAF-IBETA, Patient, Material, bacterial transcription, multiple colorectal, Cells, Cistron, inherited genetic, TAF-Ibeta, nuclear hormone receptor, Dengue Viruses, Classical, i2pp2a, HSPABP2, genetic susceptibilities, other disease, Classical Dengue Fevers, Dengue Fever, Transcriptome Profile, THP-1 Cell, 2210017D18Rik, dCHIP, vitamin D receptor activity, Gene, SCAR16, genetic predisposition, PHAPII, ligand-dependent nuclear receptor activity, Nr2b1, 9530071D11Rik, Susceptibility, DmelCG5203, Metabolism, disease or disorder, THP-1 Cell Lines, OSBP9, familial adenomatous polyposis, MAP, THP-1 Cell Line, study, vitamin D3 receptor activity, NY-CO-7, lipid metabolism, Genetic, Viruses, familial adenomatous polyposis 2, Profile, weak, ipp2a2, 2pp2a, interferon secretion, clinical infection, CG10574, vitamin A receptor activity, non-neoplastic, autosomal recessive multiple colorectal adenomas, Infestation and Infection, Break-bone fever, 2PP2A, Predispositions, taf-ibeta, 65K, Clients, Nationality, DmelCG3924, CG42257, Dmel_CG30327, dSET, dSet, disorder, THP 1 Cell Line, snp, UBOX1, African unspecified, 0610033N24Rik, THP 1 Cells, constitutitional genetic, PP1131, androgen receptor activity, Disease, cg11478, Transcriptome, OPR-10, MUTYH-Associated Polyposis, estrogen-activated sequence-specific DNA binding, disorders, igaad, CG5203, Cell Lines, Ethnic Groups, Infectious, cytokine metabolic process, medical condition, l(2)04405, Cistrons, genetic susceptibility, Client, Cell, group, Classical Dengue, I-2PP2A, chemical analysis, Dm I-2, Gene Expression Signatures, Singapore hemorrhagic fever, I2PP2A, Infection, classical dengue, RNA polymerase II transcription factor activity, condition, Gene Expression Signature, Breakbone Fever Virus, Genetic Predispositions, glucocorticoid-activated sequence-specific DNA binding, THP-1, susceptibility, ensemble, Ldb, LDB, ORP10, Chromatin Immunoprecipitation, patient, MYH-Associated Polyposis, CG3924, predispositions, Susceptibilities, cytokine biosynthetic process, dSET/TAF-Ibeta, 2610030F17Rik, Dengue, dLDB/Chip, Classical Dengue Fever, Gene Expression Profiles, NR2B1, Genetic Susceptibility, MAP syndrome, assay, Signature, reverse transcription polymerase chain reaction, AA407739, susceptibilities, hereditary, hypothesis, FAP2, colorectal adenomatous polyposis"],"additional_accession":[]},"is_claimable":false,"name":"GWAS data (Illumina 2.5 M SNPs) in Cuban cohorts of dengue disease","description":"Data Access Committee EGAC00001000601","dates":{"output":"2025-1-9"},"accession":"EGAC00001000601","cross_references":{"TAXONOMY":["9606"],"pubmed":["28241052"],"EGA":["EGAS00001002276","EGAD00010001198"]}}