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Common Variants in Alzheimer’s Disease and Risk Stratification by Polygenic Risk Scores

dc.contributor.authorDe Rojas, Itziar
dc.contributor.authorEADB contributors
dc.contributor.authorThe GR@ACE study group
dc.contributor.authorDEGESCO consortium
dc.contributor.authorIGAP (ADGC, CHARGE, EADI, GERAD)
dc.contributor.authorPGC-ALZ consortia
dc.contributor.authorLópez de Munain Arregui, Adolfo José
dc.date.accessioned2021-06-25T07:56:46Z
dc.date.available2021-06-25T07:56:46Z
dc.date.issued2021-06-07
dc.identifier.citationNature Communications 12(1) : (2021) // Article ID 3417es_ES
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/10810/52011
dc.description.abstractGenetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n=409,435 and validation size n=58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease.es_ES
dc.description.sponsorshipThe present work has been performed as part of the doctoral program of I. de Rojas at the Universitat de Barcelona (Barcelona, Spain) supported by national grant from the Instituto de Salud Carlos III FI20/00215. The Genome Research @ Fundació ACE project (GR@ACE) is supported by Grifols SA, Fundación bancaria “La Caixa”, Fundació ACE, and CIBERNED. A.R. and M.B. receive support from the European Union/EFPIA Innovative Medicines Initiative Joint undertaking ADAPTED and MOPEAD projects (grant numbers 115975 and 115985, respectively). M.B. and A.R. are also supported by national grants PI13/02434, PI16/01861, PI17/01474, PI19/01240 and PI19/01301. Acción Estratégica en Salud is integrated into the Spanish National R + D + I Plan and funded by ISCIII (Instituto de Salud Carlos III)—Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER—“Una manera de hacer Europa”). The Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting VUmc fonds. The clinical database structure was developed with funding from Stichting Dioraphte. Genotyping of the Dutch case-control samples was performed in the context of EADB (European Alzheimer DNA biobank) funded by the JPco-fuND FP-829-029 (ZonMW project number 733051061). 100-Plus study. This work was supported by Stichting Alzheimer Nederland (WE09.2014-03), Stichting Diorapthe, horstingstuit foundation, Memorabel (ZonMW project number 733050814, 733050512) and Stichting VUmc Fonds. Genotyping of the 100-Plus Study was performed in the context of EADB (European Alzheimer DNA biobank) funded by the JPco-fuND FP-829-029 (ZonMW project numb 733051061). Longitudinal Aging Study Amsterdam (LASA) is largely supported by a grant from the Netherlands Ministry of Health, Welfare and Sports, Directorate of LongTerm Care. This work was supported by a grant (European Alzheimer DNA BioBank, EADB) from the EU Joint Program—Neurodegenerative Disease Research (JPND) and also funded by Inserm, Institut Pasteur de Lille, the Lille Métropole Communauté Urbaine, the French government’s LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to AD). Genotyping of the German case-control samples was performed in the context of EADB (European Alzheimer DNA biobank) funded by the JPco-fuND (German Federal Ministry of Education and Research, BMBF: 01ED1619A). The i–Select chips was funded by the French National Foundation on AD and related disorders. EADI was supported by the LABEX (laboratory of excellence program investment for the future) DISTALZ grant, Inserm, Institut Pasteur de Lille, Université de Lille 2 and the Lille University Hospital. GERAD was supported by the Medical Research Council (Grant n° 503480), Alzheimer’s Research UK (Grant n° 503176), the Wellcome Trust (Grant n° 082604/2/07/Z) and German Federal Ministry of Education and Research (BMBF): Competence Network Dementia (CND) grant n° 01GI0102, 01GI0711, 01GI0420. CHARGE was partly supported by the NIA/NHLBI grants AG049505, AG058589, HL105756 and AGES contract N01–AG–12100, the Icelandic Heart Association, and the Erasmus Medical Center and Erasmus University. ADGC was supported by the NIH/NIA grants: U01 AG032984, U24 AG021886, U01 AG016976, and the Alzheimer’s Association grant ADGC–10–196728es_ES
dc.language.isoenges_ES
dc.publisherSpringeres_ES
dc.relationinfo:eu-repo/grantAgreement/EC/H2020/115975es_ES
dc.relationinfo:eu-repo/grantAgreement/EC/H2020/115985es_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/es/*
dc.subjectalzheimer's diseasees_ES
dc.subjectpolygenetic riskes_ES
dc.subjectpreventive and curative clinical trialses_ES
dc.subjectSHARPIN genees_ES
dc.subjectstratifying by APOEes_ES
dc.subjectindividuals at high riskes_ES
dc.titleCommon Variants in Alzheimer’s Disease and Risk Stratification by Polygenic Risk Scoreses_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.rights.holderThis article is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0)es_ES
dc.relation.publisherversionhttps://www.nature.com/articles/s41467-021-22491-8es_ES
dc.identifier.doi10.1038/s41467-021-22491-8
dc.contributor.funderEuropean Commission
dc.departamentoesNeurocienciases_ES
dc.departamentoeuNeurozientziakes_ES


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