Genetic associations between modifiable risk factors and Alzheimer disease
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2023 |
| Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10451/57729 |
Resumo: | © 2023 European Alzheimer’s & Dementia Biobank Mendelian Randomization (EADB-MR) Collaboration. JAMA Network Open. Open Access: This is an open access article distributed under the terms of the CC-BY License |
| id |
RCAP_1410f77001c7f4dc865051566bafd55c |
|---|---|
| oai_identifier_str |
oai:repositorio.ul.pt:10451/57729 |
| network_acronym_str |
RCAP |
| network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| repository_id_str |
7160 |
| spelling |
Genetic associations between modifiable risk factors and Alzheimer disease© 2023 European Alzheimer’s & Dementia Biobank Mendelian Randomization (EADB-MR) Collaboration. JAMA Network Open. Open Access: This is an open access article distributed under the terms of the CC-BY LicenseImportance: An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia. Objective: To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention. Design, setting, and participants: This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for AD were obtained from the European Alzheimer & Dementia Biobank (EADB), generated on August 31, 2021. Main analyses were conducted using the EADB clinically diagnosed end point data. All analyses were performed between April 12 and October 27, 2022. Exposures: Genetically determined modifiable risk factors. Main outcomes and measures: Odds ratios (ORs) and 95% CIs for AD were calculated per 1-unit change of genetically determined risk factors. Results: The EADB-diagnosed cohort included 39 106 participants with clinically diagnosed AD and 401 577 control participants without AD. The mean age ranged from 72 to 83 years for participants with AD and 51 to 80 years for control participants. Among participants with AD, 54% to 75% were female, and among control participants, 48% to 60% were female. Genetically determined high-density lipoprotein (HDL) cholesterol concentrations were associated with increased odds of AD (OR per 1-SD increase, 1.10 [95% CI, 1.05-1.16]). Genetically determined high systolic blood pressure was associated with increased risk of AD after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.22 [95% CI, 1.02-1.46]). In a second analysis to minimize bias due to sample overlap, the entire UK Biobank was excluded from the EADB consortium; odds for AD were similar for HDL cholesterol (OR per 1-SD unit increase, 1.08 [95% CI, 1.02-1.15]) and systolic blood pressure after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.23 [95% CI, 1.01-1.50]). Conclusions and relevance: This genetic association study found novel genetic associations between high HDL cholesterol concentrations and high systolic blood pressure with higher risk of AD. These findings may inspire new drug targeting and improved prevention implementation.Dr Frikke-Schmidt was funded by grants from the Lundbeck Foundation (grant No. R278-2018-804), the Danish Heart Foundation, and Innovation Fund Denmark (grant No. 9084-00020B).American Medical AssociationRepositório da Universidade de LisboaLuo, JiaoThomassen, Jesper QvistBellenguez, CélineGrenier-Boley, Benjaminde Rojas, ItziarCastillo, AtahualpaParveen, KayenatKüçükali, FahriNicolas, AudePeters, OliverSchneider, AnjaDichgans, MartinRujescu, DanScherbaum, NorbertJürgen, DeckertRiedel-Heller, SteffiHausner, LucreziaPorcel, Laura MolinaDüzel, EmrahGrimmer, TimoWiltfang, JensHeilmann-Heimbach, StefanieMoebus, SusanneTegos, ThomasScarmeas, NikolaosClarimon, JordiMoreno, FerminPérez-Tur, JordiBullido, María J.Pastor, PauSánchez-Valle, RaquelÁlvarez, VictoriaBoada, MercèGarcía-González, PabloPuerta, RaquelMir, PabloReal, Luis M.Piñol-Ripoll, GerardGarcía-Alberca, Jose MaríaRoyo, Jose LuísRodriguez-Rodriguez, EloySoininen, HilkkaKuulasmaa, TeemuDe Mendonça, AlexandreMehrabian, ShimaHort, JakubVyhnalek, Martinvan der Lee, SvenGraff, CarolinePapenberg, GoranGiedraitis, VilmantasBoland, AnneBacq-Daian, DelphineDeleuze, Jean-FrançoisNicolas, GaelDufouil, CarolePasquier, FlorenceHanon, OlivierDebette, StéphanieGrünblatt, EdnaPopp, JuliusBenussi, LuisaGalimberti, DanielaArosio, BeatriceMecocci, PatriziaSolfrizzi, VincenzoParnetti, LucillaSquassina, AlessioTremolizzo, LucioBorroni, BarbaraNacmias, BenedettaSorbi, SandroCaffarra, PaoloSeripa, DavideRainero, InnocenzoDaniele, AntonioMasullo, CarloSpalletta, GianfrancoWilliams, JulieAmouyel, PhilippeJessen, FrankKehoe, PatrickMagda, TsolakiRossi, GiacominaSánchez-Juan, PascualSleegers, KristelIngelsson, MartinAndreassen, Ole A.Hiltunen, MikkoVan Duijn, CorneliaSims, Rebeccavan der Flier, WiesjeRuiz, AgustínRamirez, AlfredoLambert, Jean-CharlesFrikke-Schmidt, Ruth2023-05-31T14:18:59Z20232023-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/57729engJAMA Netw Open. 2023 May 1;6(5):e231373410.1001/jamanetworkopen.2023.137342574-3805info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T17:06:32Zoai:repositorio.ul.pt:10451/57729Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:08:15.219665Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Genetic associations between modifiable risk factors and Alzheimer disease |
| title |
Genetic associations between modifiable risk factors and Alzheimer disease |
| spellingShingle |
Genetic associations between modifiable risk factors and Alzheimer disease Luo, Jiao |
| title_short |
Genetic associations between modifiable risk factors and Alzheimer disease |
| title_full |
Genetic associations between modifiable risk factors and Alzheimer disease |
| title_fullStr |
Genetic associations between modifiable risk factors and Alzheimer disease |
| title_full_unstemmed |
Genetic associations between modifiable risk factors and Alzheimer disease |
| title_sort |
Genetic associations between modifiable risk factors and Alzheimer disease |
| author |
Luo, Jiao |
| author_facet |
Luo, Jiao Thomassen, Jesper Qvist Bellenguez, Céline Grenier-Boley, Benjamin de Rojas, Itziar Castillo, Atahualpa Parveen, Kayenat Küçükali, Fahri Nicolas, Aude Peters, Oliver Schneider, Anja Dichgans, Martin Rujescu, Dan Scherbaum, Norbert Jürgen, Deckert Riedel-Heller, Steffi Hausner, Lucrezia Porcel, Laura Molina Düzel, Emrah Grimmer, Timo Wiltfang, Jens Heilmann-Heimbach, Stefanie Moebus, Susanne Tegos, Thomas Scarmeas, Nikolaos Clarimon, Jordi Moreno, Fermin Pérez-Tur, Jordi Bullido, María J. Pastor, Pau Sánchez-Valle, Raquel Álvarez, Victoria Boada, Mercè García-González, Pablo Puerta, Raquel Mir, Pablo Real, Luis M. Piñol-Ripoll, Gerard García-Alberca, Jose María Royo, Jose Luís Rodriguez-Rodriguez, Eloy Soininen, Hilkka Kuulasmaa, Teemu De Mendonça, Alexandre Mehrabian, Shima Hort, Jakub Vyhnalek, Martin van der Lee, Sven Graff, Caroline Papenberg, Goran Giedraitis, Vilmantas Boland, Anne Bacq-Daian, Delphine Deleuze, Jean-François Nicolas, Gael Dufouil, Carole Pasquier, Florence Hanon, Olivier Debette, Stéphanie Grünblatt, Edna Popp, Julius Benussi, Luisa Galimberti, Daniela Arosio, Beatrice Mecocci, Patrizia Solfrizzi, Vincenzo Parnetti, Lucilla Squassina, Alessio Tremolizzo, Lucio Borroni, Barbara Nacmias, Benedetta Sorbi, Sandro Caffarra, Paolo Seripa, Davide Rainero, Innocenzo Daniele, Antonio Masullo, Carlo Spalletta, Gianfranco Williams, Julie Amouyel, Philippe Jessen, Frank Kehoe, Patrick Magda, Tsolaki Rossi, Giacomina Sánchez-Juan, Pascual Sleegers, Kristel Ingelsson, Martin Andreassen, Ole A. Hiltunen, Mikko Van Duijn, Cornelia Sims, Rebecca van der Flier, Wiesje Ruiz, Agustín Ramirez, Alfredo Lambert, Jean-Charles Frikke-Schmidt, Ruth |
| author_role |
author |
| author2 |
Thomassen, Jesper Qvist Bellenguez, Céline Grenier-Boley, Benjamin de Rojas, Itziar Castillo, Atahualpa Parveen, Kayenat Küçükali, Fahri Nicolas, Aude Peters, Oliver Schneider, Anja Dichgans, Martin Rujescu, Dan Scherbaum, Norbert Jürgen, Deckert Riedel-Heller, Steffi Hausner, Lucrezia Porcel, Laura Molina Düzel, Emrah Grimmer, Timo Wiltfang, Jens Heilmann-Heimbach, Stefanie Moebus, Susanne Tegos, Thomas Scarmeas, Nikolaos Clarimon, Jordi Moreno, Fermin Pérez-Tur, Jordi Bullido, María J. Pastor, Pau Sánchez-Valle, Raquel Álvarez, Victoria Boada, Mercè García-González, Pablo Puerta, Raquel Mir, Pablo Real, Luis M. Piñol-Ripoll, Gerard García-Alberca, Jose María Royo, Jose Luís Rodriguez-Rodriguez, Eloy Soininen, Hilkka Kuulasmaa, Teemu De Mendonça, Alexandre Mehrabian, Shima Hort, Jakub Vyhnalek, Martin van der Lee, Sven Graff, Caroline Papenberg, Goran Giedraitis, Vilmantas Boland, Anne Bacq-Daian, Delphine Deleuze, Jean-François Nicolas, Gael Dufouil, Carole Pasquier, Florence Hanon, Olivier Debette, Stéphanie Grünblatt, Edna Popp, Julius Benussi, Luisa Galimberti, Daniela Arosio, Beatrice Mecocci, Patrizia Solfrizzi, Vincenzo Parnetti, Lucilla Squassina, Alessio Tremolizzo, Lucio Borroni, Barbara Nacmias, Benedetta Sorbi, Sandro Caffarra, Paolo Seripa, Davide Rainero, Innocenzo Daniele, Antonio Masullo, Carlo Spalletta, Gianfranco Williams, Julie Amouyel, Philippe Jessen, Frank Kehoe, Patrick Magda, Tsolaki Rossi, Giacomina Sánchez-Juan, Pascual Sleegers, Kristel Ingelsson, Martin Andreassen, Ole A. Hiltunen, Mikko Van Duijn, Cornelia Sims, Rebecca van der Flier, Wiesje Ruiz, Agustín Ramirez, Alfredo Lambert, Jean-Charles Frikke-Schmidt, Ruth |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Luo, Jiao Thomassen, Jesper Qvist Bellenguez, Céline Grenier-Boley, Benjamin de Rojas, Itziar Castillo, Atahualpa Parveen, Kayenat Küçükali, Fahri Nicolas, Aude Peters, Oliver Schneider, Anja Dichgans, Martin Rujescu, Dan Scherbaum, Norbert Jürgen, Deckert Riedel-Heller, Steffi Hausner, Lucrezia Porcel, Laura Molina Düzel, Emrah Grimmer, Timo Wiltfang, Jens Heilmann-Heimbach, Stefanie Moebus, Susanne Tegos, Thomas Scarmeas, Nikolaos Clarimon, Jordi Moreno, Fermin Pérez-Tur, Jordi Bullido, María J. Pastor, Pau Sánchez-Valle, Raquel Álvarez, Victoria Boada, Mercè García-González, Pablo Puerta, Raquel Mir, Pablo Real, Luis M. Piñol-Ripoll, Gerard García-Alberca, Jose María Royo, Jose Luís Rodriguez-Rodriguez, Eloy Soininen, Hilkka Kuulasmaa, Teemu De Mendonça, Alexandre Mehrabian, Shima Hort, Jakub Vyhnalek, Martin van der Lee, Sven Graff, Caroline Papenberg, Goran Giedraitis, Vilmantas Boland, Anne Bacq-Daian, Delphine Deleuze, Jean-François Nicolas, Gael Dufouil, Carole Pasquier, Florence Hanon, Olivier Debette, Stéphanie Grünblatt, Edna Popp, Julius Benussi, Luisa Galimberti, Daniela Arosio, Beatrice Mecocci, Patrizia Solfrizzi, Vincenzo Parnetti, Lucilla Squassina, Alessio Tremolizzo, Lucio Borroni, Barbara Nacmias, Benedetta Sorbi, Sandro Caffarra, Paolo Seripa, Davide Rainero, Innocenzo Daniele, Antonio Masullo, Carlo Spalletta, Gianfranco Williams, Julie Amouyel, Philippe Jessen, Frank Kehoe, Patrick Magda, Tsolaki Rossi, Giacomina Sánchez-Juan, Pascual Sleegers, Kristel Ingelsson, Martin Andreassen, Ole A. Hiltunen, Mikko Van Duijn, Cornelia Sims, Rebecca van der Flier, Wiesje Ruiz, Agustín Ramirez, Alfredo Lambert, Jean-Charles Frikke-Schmidt, Ruth |
| description |
© 2023 European Alzheimer’s & Dementia Biobank Mendelian Randomization (EADB-MR) Collaboration. JAMA Network Open. Open Access: This is an open access article distributed under the terms of the CC-BY License |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2023-05-31T14:18:59Z 2023 2023-01-01T00:00:00Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/57729 |
| url |
http://hdl.handle.net/10451/57729 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
JAMA Netw Open. 2023 May 1;6(5):e2313734 10.1001/jamanetworkopen.2023.13734 2574-3805 |
| dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
American Medical Association |
| publisher.none.fl_str_mv |
American Medical Association |
| dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
| instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
| instacron_str |
RCAAP |
| institution |
RCAAP |
| reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
| repository.mail.fl_str_mv |
|
| _version_ |
1799134636465455104 |