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Genome-wide association study meta-analysis of neurofilament light (NfL) levels in blood reveals novel loci related to neurodegeneration

dc.rights.licenseopenen_US
dc.contributor.authorAHMAD, Shahzad
dc.contributor.authorIMTIAZ, Mohammad Aslam
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorMISHRA, Aniket
dc.contributor.authorWANG, Ruiqi
dc.contributor.authorHERRERA-RIVERO, Marisol
dc.contributor.authorBIS, Joshua C
dc.contributor.authorFORNAGE, Myriam
dc.contributor.authorROSHCHUPKIN, Gennady
dc.contributor.authorHOFER, Edith
dc.contributor.authorLOGUE, Mark
dc.contributor.authorLONGSTRETH, W T Jr
dc.contributor.authorXIA, Rui
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorBOUTELOUP, Vincent
dc.contributor.authorMOSLEY, Thomas
dc.contributor.authorLAUNER, Lenore J
dc.contributor.authorKHALIL, Michael
dc.contributor.authorKUHLE, Jens
dc.contributor.authorRISSMAN, Robert A
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorCHENE, Genevieve
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDUFOUIL, Carole
dc.contributor.authorDJOUSSE, Luc
dc.contributor.authorLYONS, Michael J
dc.contributor.authorMUKAMAL, Kenneth J
dc.contributor.authorKREMEN, William S
dc.contributor.authorFRANZ, Carol E
dc.contributor.authorSCHMIDT, Reinhold
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDEBETTE, Stephanie
dc.contributor.authorBRETELER, Monique M B
dc.contributor.authorBERGER, Klaus
dc.contributor.authorYANG, Qiong
dc.contributor.authorSESHADRI, Sudha
dc.contributor.authorAZIZ, N Ahmad
dc.contributor.authorGHANBARI, Mohsen
dc.contributor.authorIKRAM, M Arfan
dc.date.accessioned2024-10-21T10:59:07Z
dc.date.available2024-10-21T10:59:07Z
dc.date.issued2024-09-09
dc.identifier.issn2399-3642en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/202599
dc.description.abstractEnNeurofilament light chain (NfL) levels in circulation have been established as a sensitive biomarker of neuro-axonal damage across a range of neurodegenerative disorders. Elucidation of the genetic architecture of blood NfL levels could provide new insights into molecular mechanisms underlying neurodegenerative disorders. In this meta-analysis of genome-wide association studies (GWAS) of blood NfL levels from eleven cohorts of European ancestry, we identify two genome-wide significant loci at 16p12 (UMOD) and 17q24 (SLC39A11). We observe association of three loci at 1q43 (FMN2), 12q14, and 12q21 with blood NfL levels in the meta-analysis of African-American ancestry. In the trans-ethnic meta-analysis, we identify three additional genome-wide significant loci at 1p32 (FGGY), 6q14 (TBX18), and 4q21. In the post-GWAS analyses, we observe the association of higher NfL polygenic risk score with increased plasma levels of total-tau, A beta-40, A beta-42, and higher incidence of Alzheimer's disease in the Rotterdam Study. Furthermore, Mendelian randomization analysis results suggest that a lower kidney function could cause higher blood NfL levels. This study uncovers multiple genetic loci of blood NfL levels, highlighting the genes related to molecular mechanism of neurodegeneration. An ancestry-specific and trans-ethnic meta-analysis of Genome-wide Association Study of blood NfL levels identified multiple loci related to neurodegeneration and potential causal association between reduced kidney function and higher blood NfL levels.
dc.description.sponsorshipStopping cognitive decline and dementia by fighting covert cerebral small vessel diseaseen_US
dc.description.sponsorshipVaincre les maladies vasculaires cérébrales par un nouveau paradigme de prévention de précision et d'innovation thérapeutiqueen_US
dc.description.sponsorshipInitiative pour la résilience du cerveau : les gènes qui protègent le cerveau des agressions cérébrovasculairesen_US
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.title.enGenome-wide association study meta-analysis of neurofilament light (NfL) levels in blood reveals novel loci related to neurodegeneration
dc.title.alternativeCommun Biolen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1038/s42003-024-06804-3en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed39251807en_US
bordeaux.journalCommunications Biologyen_US
bordeaux.page1103en_US
bordeaux.volume7en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue1en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamPHARES_BPHen_US
bordeaux.teamELEANOR_BPHen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDFondation Plan Alzheimeren_US
bordeaux.identifier.funderIDFondation Vaincre Alzheimeren_US
bordeaux.identifier.funderIDFondation pour la Recherche Médicaleen_US
hal.identifierhal-04746261
hal.version1
hal.date.transferred2024-10-21T10:59:12Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Communications%20Biology&rft.date=2024-09-09&rft.volume=7&rft.issue=1&rft.spage=1103&rft.epage=1103&rft.eissn=2399-3642&rft.issn=2399-3642&rft.au=AHMAD,%20Shahzad&IMTIAZ,%20Mohammad%20Aslam&MISHRA,%20Aniket&WANG,%20Ruiqi&HERRERA-RIVERO,%20Marisol&rft.genre=article


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