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Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk

dc.contributor.authorJansen, Iris E.
dc.contributor.authorSavage, Jeanne E.
dc.contributor.authorWatanabe, Kyoko
dc.contributor.authorBryois, Julien
dc.contributor.authorWilliams, Dylan M.
dc.contributor.authorSteinberg, Stacy
dc.contributor.authorSealock, Julia
dc.contributor.authorKarlsson, Ida K.
dc.contributor.authorHägg, Sara
dc.contributor.authorAthanasiu, Lavinia
dc.contributor.authorVoyle, Nicola
dc.contributor.authorProitsi, Petroula
dc.contributor.authorWitoelar, Aree
dc.contributor.authorStringer, Sven
dc.contributor.authorAarsland, Dag
dc.contributor.authorAlmdahl, Ina Selseth
dc.contributor.authorAndersen, Fred
dc.contributor.authorBergh, Sverre
dc.contributor.authorBettella, Francesco
dc.contributor.authorBjörnsson, Sigurbjörn
dc.contributor.authorBrækhus, Anne
dc.contributor.authorBråthen, Geir
dc.contributor.authorde Leeuw, Christiaan A.
dc.contributor.authorDesikan, Rahul S.
dc.contributor.authorDjurovic, Srdjan
dc.contributor.authorDumitrescu, Logan
dc.contributor.authorFladby, Tormod
dc.contributor.authorHohman, Timothy J.
dc.contributor.authorJónsson, Pálmi V.
dc.contributor.authorKiddle, Steven J
dc.contributor.authorRongve, Arvid
dc.contributor.authorSaltvedt, Ingvild
dc.contributor.authorSando, Sigrid Botne
dc.contributor.authorSelbæk, Geir
dc.contributor.authorShoai, Maryam
dc.contributor.authorSkene, Nathan G.
dc.contributor.authorSnædal, Jón G.
dc.contributor.authorStordal, Eystein
dc.contributor.authorUlstein, Ingun
dc.contributor.authorWang, Yunpeng
dc.contributor.authorWhite, Linda Rosemary
dc.contributor.authorHardy, John
dc.contributor.authorHjerling-Leffler, Jens
dc.contributor.authorSullivan, Patrick
dc.contributor.authorvan der Flier, Wiesje M.
dc.contributor.authorDobson, Richard
dc.contributor.authorDavis, Lea K
dc.contributor.authorStefánsson, Hreinn
dc.contributor.authorStefánsson, Kári
dc.contributor.authorPedersen, Nancy L
dc.contributor.authorRipke, Stephan
dc.contributor.authorAndreassen, Ole Andreas
dc.contributor.authorPosthuma, Danielle
dc.date.accessioned2020-02-04T10:17:11Z
dc.date.available2020-02-04T10:17:11Z
dc.date.issued2019-01-07
dc.description.abstractAlzheimer’s disease (AD) is highly heritable and recent studies have identified over 20 disease-associated genomic loci. Yet these only explain a small proportion of the genetic variance, indicating that undiscovered loci remain. Here, we performed a large genome-wide association study of clinically diagnosed AD and AD-by-proxy (71,880 cases, 383,378 controls). AD-by-proxy, based on parental diagnoses, showed strong genetic correlation with AD (r<sub>g</sub> = 0.81). Meta-analysis identified 29 risk loci, implicating 215 potential causative genes. Associated genes are strongly expressed in immune-related tissues and cell types (spleen, liver, and microglia). Gene-set analyses indicate biological mechanisms involved in lipid-related processes and degradation of amyloid precursor proteins. We show strong genetic correlations with multiple health-related outcomes, and Mendelian randomization results suggest a protective effect of cognitive ability on AD risk. These results are a step forward in identifying the genetic factors that contribute to AD risk and add novel insights into the neurobiology of AD.en_US
dc.identifier.citationJansen, I.E., Savage, J.E., Watanabe, K., Bryois, J., Williams, D.M., Steinberg, S., ... Posthuma, D. (2019). Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk. <i>Nature Genetics, 51</i>(3), 404-413. https://doi.org/10.1038/s41588-018-0311-9en_US
dc.identifier.cristinIDFRIDAID 1656853
dc.identifier.doi10.1038/s41588-018-0311-9
dc.identifier.issn1061-4036
dc.identifier.issn1546-1718
dc.identifier.urihttps://hdl.handle.net/10037/17318
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.relation.journalNature Genetics
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/FRIMEDBIO/251134/Norway/Boosting the power of genetics in mental health with new statistical tools//en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/BEHANDLING/248778/Norway/Identifying the missing heritability of complex diseases leveraging biobanks, registries and novel analytical tools in psychiatric disorders//en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/SFF/223273/Norway/Norwegian Centre for Mental Disorders Research/NORMENT/en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/FRIMEDBIO/213837/Norway/Genetic influence on brain phenotypes. Implications for disease mechanisms in severe mental disorders//en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/BEHANDLING/225989/Norway/Identifying the polygenic architecture of dementia leveraging new statistical methods//en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holder© The Author(s), under exclusive licence to Springer Nature America, Inc. 2019en_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Geriatrics: 778en_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Geriatri: 778en_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical genetics: 714en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk genetikk: 714en_US
dc.titleGenome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risken_US
dc.type.versionacceptedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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