biostudies-literatureJansen IEEuropean Research CouncilEU Joint Programme – Neurodegenerative Disease ResearchNIA NIH HHSDutch Research Council (NWO)ZonMw821-842https://www.ebi.ac.uk/biostudies/studies/S-EPMC9547780biostudies-literatureUnknown144(5)Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n = 8074; replication n = 5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for Aβ42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple Aβ42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.Acta neuropathologicaGenome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers.PMC9547780024.004.012R01 AG01580173305095007RF1 AG058501733051061834057RF1 AG053303R01 AG058501720931R01 AG044546R01 AG068398P30 AG066444U01 AG058922681712R01 AG064877R01 AG064614P01 AG003991European Alzheimer DNA BioBank, EADBFrolich LScheltens Pvan der Flier WTesi NGomez-Fonseca DKucukali FJansen IEVan Dongen JScherbaum NDalmasso MCAthanasiu LLaske CPopp JSung YJShadrin AKern SMol MOWaern MPosthuma DCruchaga Cde Munain ALBahrami SClarimon JSoininen HHerukka SKLleo ABiessels GJFladby TGobom JLopez-Garcia SLeinonen VMoreno FEngelborghs SKleineidam LSanchez-Juan PVidal JSBoland AHaapasalo APasquier FSchneider ARamirez ADufouil CHampel HZettergren AWightman DPSelbæk GAlcolea DGarcia-Gonzalez PVogelgsang JBelbin Ode Rojas IBertram LLambert JCVandenberghe RZulaica MMishra AQuintela Ide Deyn PPRuiz AVisser PJTeunissen CEVan Broeckhoven CAndrade VOrellana APijnenburg YALNothen MMRamakers IZetterberg HAmouyel PHelisalmi SKnapskog ABWittens MMJAndreassen OAHolstege HHernandez Ivan Swieten JCKornhuber JBellenguez CPeters OPuerta RDiehl-Schmid JGrimmer TLage CTarraga LJessen FWagner MBjerke MCarracedo AWiltfang JEADB consortiumBailly HTeipel SDebette Svan Duijn CMFortea JLewczuk PSelnes PCervera-Carles LDeleuze JFBoada MHausner LHeilmann-Heimbach SHiltunen MPalhaugen LBlennow KDuzel ESleegers KKoivisto AMGoldhardt OMarquie MJarholm JHanon OSchmid MBlesa RPerneczky RPapma JMDjurovic SBuerger KNicolas GVromen EMPriller JIngelsson Mvan der Lee SJAlvarez IChene GClaassen JAHRGarcia-Martinez MMaier WBergh SMontrreal LGrenier-Boley BPastor PAlegret MDuron EGiegling IAli MRujescu DDols-Icardo OHeneka MTKuulasmaa TPozueta ARodriguez-Rodriguez ESkoog ITsolaki MMoreno-Grau SSaltvedt ITijms BGR@ACE study groupfalseGenome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers.Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n = 8074; replication n = 5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for Aβ42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple Aβ42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.2022-01-01T00:00:00Z2022 Nov2026-06-01T02:11:03.08Z2025-02-19T01:28:35.178ZS-EPMC95477803606663310.1007/s00401-022-02454-z