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Multi-omics and pathway analyses of genome-wide associations implicate regulation and immunity in verbal declarative memory performance

dc.rights.licenseopenen_US
dc.contributor.authorMEI, Hao
dc.contributor.authorSIMINO, Jeannette
dc.contributor.authorLI, Lianna
dc.contributor.authorJIANG, Fan
dc.contributor.authorBIS, Joshua C
dc.contributor.authorDAVIES, Gail
dc.contributor.authorHILL, W David
dc.contributor.authorXIA, Charley
dc.contributor.authorGUDNASON, Vilmundur
dc.contributor.authorYANG, Qiong
dc.contributor.authorLAHTI, Jari
dc.contributor.authorSMITH, Jennifer A
dc.contributor.authorKIRIN, Mirna
dc.contributor.authorDE JAGER, Philip
dc.contributor.authorARMSTRONG, Nicola J
dc.contributor.authorGHANBARI, Mohsen
dc.contributor.authorKOLCIC, Ivana
dc.contributor.authorMORAN, Christopher
dc.contributor.authorTEUMER, Alexander
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorSARGURUPREMRAJ, Murali
dc.contributor.authorMAHMUD, Shamsed
dc.contributor.authorFORNAGE, Myriam
dc.contributor.authorZHAO, Wei
dc.contributor.authorSATIZABAL, Claudia L
dc.contributor.authorPOLASEK, Ozren
dc.contributor.authorRAIKKONEN, Katri
dc.contributor.authorLIEWALD, David C
dc.contributor.authorHOMUTH, Georg
dc.contributor.authorCALLISAYA, Michele
dc.contributor.authorMATHER, Karen A
dc.contributor.authorWINDHAM, B Gwen
dc.contributor.authorZEMUNIK, Tatijana
dc.contributor.authorPALOTIE, Aarno
dc.contributor.authorPATTIE, Alison
dc.contributor.authorVAN DER AUWERA, Sandra
dc.contributor.authorTHALAMUTHU, Anbupalam
dc.contributor.authorKNOPMAN, David S
dc.contributor.authorRUDAN, Igor
dc.contributor.authorSTARR, John M
dc.contributor.authorWITTFELD, Katharina
dc.contributor.authorKOCHAN, Nicole A
dc.contributor.authorGRISWOLD, Michael E
dc.contributor.authorVITART, Veronique
dc.contributor.authorBRODATY, Henry
dc.contributor.authorGOTTESMAN, Rebecca
dc.contributor.authorCOX, Simon R
dc.contributor.authorPSATY, Bruce M
dc.contributor.authorBOERWINKLE, Eric
dc.contributor.authorCHASMAN, Daniel I
dc.contributor.authorGRODSTEIN, Francine
dc.contributor.authorSACHDEV, Perminder S
dc.contributor.authorSRIKANTH, Velandai
dc.contributor.authorHAYWARD, Caroline
dc.contributor.authorWILSON, James F
dc.contributor.authorERIKSSON, Johan G
dc.contributor.authorKARDIA, Sharon L R
dc.contributor.authorGRABE, Hans J
dc.contributor.authorBENNETT, David A
dc.contributor.authorIKRAM, M Arfan
dc.contributor.authorDEARY, Ian J
dc.contributor.authorVAN DUIJN, Cornelia M
dc.contributor.authorLAUNER, Lenore
dc.contributor.authorFITZPATRICK, Annette L
dc.contributor.authorSESHADRI, Sudha
dc.contributor.authorBRESSLER, Jan
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDEBETTE, Stephanie
dc.contributor.authorMOSLEY, Thomas H Jr
dc.date.accessioned2024-02-22T12:43:58Z
dc.date.available2024-02-22T12:43:58Z
dc.date.issued2024-01-20
dc.identifier.issn1758-9193en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/188312
dc.description.abstractEnBACKGROUND: Uncovering the functional relevance underlying verbal declarative memory (VDM) genome-wide association study (GWAS) results may facilitate the development of interventions to reduce age-related memory decline and dementia. METHODS: We performed multi-omics and pathway enrichment analyses of paragraph (PAR-dr) and word list (WL-dr) delayed recall GWAS from 29,076 older non-demented individuals of European descent. We assessed the relationship between single-variant associations and expression quantitative trait loci (eQTLs) in 44 tissues and methylation quantitative trait loci (meQTLs) in the hippocampus. We determined the relationship between gene associations and transcript levels in 53 tissues, annotation as immune genes, and regulation by transcription factors (TFs) and microRNAs. To identify significant pathways, gene set enrichment was tested in each cohort and meta-analyzed across cohorts. Analyses of differential expression in brain tissues were conducted for pathway component genes. RESULTS: The single-variant associations of VDM showed significant linkage disequilibrium (LD) with eQTLs across all tissues and meQTLs within the hippocampus. Stronger WL-dr gene associations correlated with reduced expression in four brain tissues, including the hippocampus. More robust PAR-dr and/or WL-dr gene associations were intricately linked with immunity and were influenced by 31 TFs and 2 microRNAs. Six pathways, including type I diabetes, exhibited significant associations with both PAR-dr and WL-dr. These pathways included fifteen MHC genes intricately linked to VDM performance, showing diverse expression patterns based on cognitive status in brain tissues. CONCLUSIONS: VDM genetic associations influence expression regulation via eQTLs and meQTLs. The involvement of TFs, microRNAs, MHC genes, and immune-related pathways contributes to VDM performance in older individuals.
dc.language.isoENen_US
dc.subject.enGenome-wide association study
dc.subject.enMemory
dc.subject.enExpression
dc.subject.enImmunity
dc.subject.enMulti-omics
dc.subject.enDelayed recall
dc.title.enMulti-omics and pathway analyses of genome-wide associations implicate regulation and immunity in verbal declarative memory performance
dc.title.alternativeAlzheimers Res Theren_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1186/s13195-023-01376-6en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed38245754en_US
bordeaux.journalAlzheimer's Research and Therapyen_US
bordeaux.page14en_US
bordeaux.volume16en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue1en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamELEANOR_BPHen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDNational Institutes of Healthen_US
hal.identifierhal-04472845
hal.version1
hal.date.transferred2024-02-22T12:44:06Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
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