4 research outputs found
The Genetic Architecture of Parkinson Disease in Spain: Characterizing Population-Specific Risk, Differential Haplotype Structures, and Providing Etiologic Insight
- Author
- Adarmes Gómez A. D.
- Aguilar Miquel
- Ahmed Sarah
- Bandres-Ciga Sara
- Barrero Francisco Javier
- Bergareche Jesús Alberto
- Bernal-Bernal Inmaculada
- Blauwendraat Cornelis
- Blazquez Marta
- Bonet-Ponce Luis
- Bonilla-Toribio Marta
- Botia Juan A.
- Brooks Janet
- Buiza-Rueda Dolores
- Buongiorno Maria Teresa
- Carrillo Fátima
- Carrión-Claro Mario
- Cerdan Debora
- Clarimón Jordi
- Clarke Carl
- Compta Yaroslau
- Croitoru Ioana
- Cámara Ana
- Dalgard Clifton L.
- Dols-Icardo Oriol
- Duarte Jacinto
- Duran Raquel
- Díez-Fairen M.
- Edsall Connor
- Escamilla-Sevilla Francisco
- Ezquerra Mario
- Feliz Cici
- Fernandez Manel
- Fernández-Santiago Rubén
- Garcia Ciara
- García-Ruíz Pedro
- Gibbs J. Raphael
- Gomez Heredia Maria Jose
- González-Aramburu Isabel
- Gorostidi Ana
- Gómez-Garre Pilar
- Hernández Dena
- Hoenicka Janet
- Infante Jon
- Jesús Maestre Silvia
- Jiménez Escrig Adriano
- Jorda Rafael
- Kim Jonggeol Jeffrey
- Kulisevsky Jaime
- Labrador Miguel Ángel
- Lopez-Sendon José Luis
- López de Munain Adolfo
- Macías García Daniel
- Martí María-José
- Martínez Torres Irene
- Martínez-Castrillo J. C.
- Marín-Lahoz Juan
- Mata Marina
- Menéndez González M.
- Mir Pablo
- Mondragon Elisabet
- Morris Huw
- Morrison Karen E.
- Muñoz Esteban
- Méndez-Del Barrio Carlota
- Mínguez-Castellanos Adolfo
- Nalls Michael A.
- Pagonabarraga-Mora Javier
- Pascual-Sedano B.
- Pastor Pau
- Perez Errazquin Francisco
- Perinán María Teresa
- Romero-Acebal Manolo
- Ruiz-Martínez Javier
- Ruz Clara
- Sabir Marya S.
- Saez-Atienzar Sara
- Sanchez Rodriguez Antonio
- Scholz Sonja
- Sierra María
- Simón-Sánchez Javier
- Singleton Andrew B.
- Suarez-San Martin Esther
- Tabernero César
- Tan Manuela
- Tartari J. P.
- Tejera-Parrado Cristina
- Tolosa Eduardo
- Valldeoriola Francesc
- Vargas-González Laura
- Vela-Desojo Lydia
- Vinagre-Aragon Ana
- Vives Francisco
- Álvarez Ignacio
- Álvarez Victoria
- Publication venue
- 'Wiley'
- Publication date
- 26/03/2020
- Field of study
Background: The Iberian Peninsula stands out as having variable levels of population admixture and isolation, making Spain an interesting setting for studying the genetic architecture of neurodegenerative diseases. Objectives: To perform the largest PD genome-wide association study restricted to a single country. Methods: We performed a GWAS for both risk of PD and age at onset in 7,849 Spanish individuals. Further analyses included population-specific risk haplotype assessments, polygenic risk scoring through machine learning, Mendelian randomization of expression, and methylation data to gain insight into disease-associated loci, heritability estimates, genetic correlations, and burden analyses. Results: We identified a novel population-specific genome-wide association study signal at PARK2 associated with age at onset, which was likely dependent on the c.155delA mutation. We replicated four genome-wide independent signals associated with PD risk, including SNCA, LRRK2, KANSL1/MAPT, and HLA-DQB1. A significant trend for smaller risk haplotypes at known loci was found compared to similar studies of non-Spanish origin. Seventeen PD-related genes showed functional consequence by two-sample Mendelian randomization in expression and methylation data sets. Long runs of homozygosity at 28 known genes/loci were found to be enriched in cases versus controls. Conclusions: Our data demonstrate the utility of the Spanish risk haplotype substructure for future fine-mapping efforts, showing how leveraging unique and diverse population histories can benefit genetic studies of complex diseases. The present study points to PARK2 as a major hallmark of PD etiology in Spain.This research was supported, in part, by the Intramural Research Program of the National Institutes of Health (National Institute on Aging, National Institute of Neurological Disorders and Stroke; project numbers: 1ZIA‐NS003154‐03, Z01‐AG000949‐02, and Z01‐ES101986). In addition, this work was supported by the Department of Defense (award W81XWH‐09‐2‐0128), The Michael J Fox Foundation for Parkinson's Research, and the ISCIII Grants PI 15/0878 (Fondos Feder) to V.A. and PI 15/01013 to J,H. This study was supported by grants from the Spanish Ministry of Economy and Competitiveness (PI14/01823, PI16/01575, PI18/01898, [SAF2006‐10126 (2006‐2009), SAF2010‐22329‐C02‐01 (2010‐2012), and SAF2013‐47939‐R (2013‐2018)]), co‐founded by ISCIII (Subdirección General de Evaluación y Fomento de la Investigación) and by Fondo Europeo de Desarrollo Regional (FEDER), the Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía (CVI‐02526, CTS‐7685), the Consejería de Salud y Bienestar Social de la Junta de Andalucía (PI‐0437‐2012, PI‐0471‐2013), the Sociedad Andaluza de Neurología, the Jacques and Gloria Gossweiler Foundation, the Fundación Alicia Koplowitz, and the Fundación Mutua Madrileña. Pilar Gómez‐Garre was supported by the “Miguel Servet” (from ISCIII16 FEDER) and “Nicolás Monardes” (from Andalusian Ministry of Health) programmes. Silvia Jesús Maestre was supported by the “Juan Rodés” programme, and Daniel Macías‐García was supported by the “Río Hortega” programme (both from ISCIII‐FEDER). Cristina Tejera Parrado was supported by VPPI‐US from the Universidad de Sevilla. This research has been conducted using samples from the HUVR‐IBiS Biobank (Andalusian Public Health System Biobank and ISCIII‐Red de Biobancos PT13/0010/0056). This work was also supported by the grant PSI2014‐57643 from the Junta de Andalucía to the CTS‐438 group and a research award from the Andalusian Society of Neurology
Moving beyond neurons:the role of cell type-specific gene regulation in Parkinson’s disease heritability
- Author
- Adarmes-Gomez A. D. (Astrid D.)
- Aguilar M. (Miquel)
- Alvarez I. (Ignacio)
- Alvarez V. (Victoria)
- Anderson T. (Tim)
- Bandres-Ciga S. (Sara)
- Bentley S. (Steven)
- Bergareche Yarza J. A. (Jesus Alberto)
- Bernal-Bernal I. (Inmaculada)
- Billingsley K. (Kimberley)
- Blauwendraat C. (Cornelis)
- Blazquez M. (Marta)
- Bonilla-Toribio M. (Marta)
- Botia J. (Juan)
- Bras J. (Jose)
- Brice A. (Alexis)
- Brockmann K. (Kathrin)
- Buiza-Rueda D. (Dolores)
- Camara A. (Ana)
- Carcel M. (Maria)
- Carlos Martinez-Castrillo J. (Juan)
- Carrillo F. (Fatima)
- Carrion-Claro M. (Mario)
- Cerdan D. (Debora)
- Chelban V. (Viorica)
- Clarimon J. (Jordi)
- Compta Y. (Yaroslau)
- Cookson M. R. (Mark R.)
- Corvol J.-C. (Jean-Christophe)
- Dalrymple-Alford J. (John)
- Danjou F. (Fabrice)
- de Munain Arregui A. L. (Adolfo Lopez)
- Diez-Fairen M. (Monica)
- Dols-Icardo O. (Oriol)
- Duarte J. (Jacinto)
- Duran R. (Raquel)
- Escamilla-Sevilla F. (Francisco)
- Escott-Price V. (Valentina)
- Ezquerra M. (Mario)
- Faghri F. (Faraz)
- Fernandez M. (Manel)
- Fernandez-Santiago R. (Ruben)
- Finkbeiner S. (Steven)
- Foltynie T. (Thomas)
- Fowdar J. (Javed)
- Gan-Or Z. (Ziv)
- Garcia C. (Ciara)
- Garcia-Ruiz P. (Pedro)
- Gasser T. (Thomas)
- Gibbs J. R. (J. Raphael)
- Giri A. (Anamika)
- Gomez Heredia M. J. (Maria Jose)
- Gomez-Garre P. (Pilar)
- Gonzalez-Aramburu I. (Isabel)
- Gorostidi Pagola A. (Ana)
- Gratten J. (Jacob)
- Guerreiro R. (Rita)
- Halliday G. (Glenda)
- Hardy J. (John)
- Henders A. K. (Anjali K.)
- Hernandez D. G. (Dena G.)
- Heutink P. (Peter)
- Hickie I. (Ian)
- Hoenicka J. (Janet)
- Holmans P. (Peter)
- Houlden H. (Henry)
- Infante J. (Jon)
- Javier Barrero F. (Francisco)
- Jesus S. (Silvia)
- Jimenez-Escrig A. (Adriano)
- Jose Marti M. (Maria)
- Kassam I. (Irfahan)
- Kennedy M. (Martin)
- Kia D. A. (Demis A.)
- Kinghorn K. J. (Kerri J.)
- Koks S. (Sulev)
- Krohan L. (Lynne)
- Kulisevsky J. (Jaime)
- Kwok J. (John)
- Labrador-Espinosa M. A. (Miguel A.)
- Leonard H. (Hampton)
- Lesage S. (Suzanne)
- Lewis P. (Patrick)
- Lewis S. (Simon)
- Lovering R. (Ruth)
- Lubbe S. (Steven)
- Luis Lopez-Sendon J. (Jose)
- Lungu C. (Codrin)
- Macias D. (Daniel)
- Majamaa K. (Kari)
- Marin J. (Juan)
- Marinus J. (Johan)
- Martinez Torres I. (Irene)
- Martinez M. (Maria)
- Mellick G. (George)
- Mencacci N. E. (Niccolo E.)
- Mendez-del-Barrio C. (Carlota)
- Menendez Gonzalez M. (Manuel)
- Middlehurst B. (Ben)
- Minguez A. (Adolfo)
- Mir P. (Pablo)
- Mok K. Y. (Kin Y.)
- Mondragon Rezola E. (Elisabet)
- Montgomery G. (Grant)
- Morris H. R. (Huw R.)
- Munoz E. (Esteban)
- Nalls M. A. (Mike A.)
- Nicolas A. (Aude)
- Noyce A. J. (Alastair J.)
- Ojo O. O. (Oluwadamilola O.)
- Okubadejo N. U. (Njideka U.)
- Pablo Tartari J. (Juan)
- Pagonabarraga J. (Javier)
- Pastor P. (Pau)
- Pearson J. (John)
- Perez Errazquin F. (Francisco)
- Perinan-Tocino T. (Teresa)
- Pihlstrom L. (Lasse)
- Pitcher T. (Toni)
- Plun-Favreau H. (Helene)
- Quinn J. (John)
- R'Bibo L. (Lea)
- Reed X. (Xylena)
- Reynolds R. H. (Regina H.)
- Rizig M. (Mie)
- Rizzu P. (Patrizia)
- Robak L. (Laurie)
- Rouleau G. A. (Guy A.)
- Ruiz-Martinez J. (Javier)
- Ruz C. (Clara)
- Ryten M. (Mina)
- Sanchez Rodriguez A. (Antonio)
- Scholz S. W. (Sonja W.)
- Schulte C. (Claudia)
- Sharma M. (Manu)
- Shulman J. M. (Joshua M.)
- Sidorenko J. (Julia)
- Sierra M. (Mara)
- Siitonen A. (Ari)
- Silburn P. A. (Peter A.)
- Simon-Sanchez J. (Javier)
- Singleton A. B. (Andrew B.)
- Suarez-Sanmartin E. (Esther)
- Taba P. (Pille)
- Tabernero C. (Cesar)
- Taliun S. A. (Sarah A. Gagliano)
- Tan M. (Manuela)
- Tejera-Parrado C. (Cristina)
- Teresa Boungiorno M. (Mara)
- Tolosa E. (Eduard)
- Trabzuni D. (Daniah)
- Tucci A. (Arianna)
- Valldeoriola F. (Francesc)
- Vallerga C. L. (Costanza L.)
- van Hilten J. J. (Jacobus J.)
- Vargas-Gonzalez L. (Laura)
- Vela L. (Lydia)
- Visscher P. M. (Peter M.)
- Vives F. (Francisco)
- Wallace L. (Leanne)
- Williams N. (Nigel)
- Wood N. W. (Nicholas W.)
- Wray N. R. (Naomi R.)
- Xue A. (Angli)
- Yang J. (Jian)
- Zhang F. (Futao)
- Zimprich A. (Alexander)
- Publication venue
- Springer Nature
- Publication date
- 01/01/2019
- Field of study
Abstract
Parkinson’s disease (PD), with its characteristic loss of nigrostriatal dopaminergic neurons and deposition of α-synuclein in neurons, is often considered a neuronal disorder. However, in recent years substantial evidence has emerged to implicate glial cell types, such as astrocytes and microglia. In this study, we used stratified LD score regression and expression-weighted cell-type enrichment together with several brain-related and cell-type-specific genomic annotations to connect human genomic PD findings to specific brain cell types. We found that PD heritability attributable to common variation does not enrich in global and regional brain annotations or brain-related cell-type-specific annotations. Likewise, we found no enrichment of PD susceptibility genes in brain-related cell types. In contrast, we demonstrated a significant enrichment of PD heritability in a curated lysosomal gene set highly expressed in astrocytic, microglial, and oligodendrocyte subtypes, and in LoF-intolerant genes, which were found highly expressed in almost all tested cellular subtypes. Our results suggest that PD risk loci do not lie in specific cell types or individual brain regions, but rather in global cellular processes detectable across several cell types
New insights into the genetic etiology of Alzheimer’s disease and related dementias
- Author
- A David Smith
- Aaltonen L.
- Aaltonen V.
- Aarno Palotie
- Aarsland D.
- Aavikko M.
- Abalos M. S.
- Abdelnour C.
- Abner E.
- Abraham R.
- Ad Adarmes-Gómez
- Adam Boxer
- Adam Ziemann
- Adams H.
- Adams P. M.
- Adarmes-Gómez A.
- Adarmes-Gómez A. D.
- Adriana Gamboa
- Adrienne L Cupples
- Adrienne Tin
- Aguilera N.
- Aguilera N.
- Aguirre A.
- Agustina Legaz
- Ahmad S.
- Aimee Pierce
- Aino Salminen
- Airi Jussila
- Aisha Khaleeq
- Aki Havulinna
- Akinyemi R. O.
- Al-Chalabi A.
- Alan B Stevens
- Alan Lerner
- Alarcón-Martín E.
- Albert M. S.
- Alberto Benussi
- Albin R. L.
- Alcolea D.
- Aldo Saenz
- Alegret M.
- Alessandra Chesi
- Alessandro Vacca
- Alexander Teumer
- Alexis Brice
- Ali M.
- Alisa Manning
- Alison E Fohner
- Allan I Levey
- Allen M.
- Allende I. R.
- Alonso M. D.
- Alonso M. D.
- Alvarez I.
- Alvarez L.
- Alvin Thomas
- Alyssa Aguirre
- Amanda Cano
- Amanda Elliott
- Amanda G Smith
- Amanda J Myers
- Amer-Ferrer G.
- Amin N.
- Ammar Al-Chalabi
- Amouyel P.
- Amy Gerrish
- Amy Williams
- Ana Mauleón
- Ana Pancho
- Anastasia Shcherban
- Anastasiou A.
- Anastasiou C.
- Anders Malarstig
- Andrade V.
- Andrea Ganna
- Andreassen O. A.
- Andreoni S.
- Andrew J Saykin
- Andrew McQuillin
- Andrew N McDavid
- Andrew P Lieberman
- Andrew Peterson
- Andrey Loboda
- André Lacour
- Angela Hodges
- Aniket Mishra
- Ann C McKee
- Anna Anastasiou
- Anna Antonell
- Anna Gailhajenet
- Anna M Karydas
- Anna Podgornaia
- Anne Lehtonen
- Anne Pitkäranta
- Anne Remes
- Annette Fitzpatrick
- Annika Auranen
- Antequera M.
- Anthony Bayer
- Anthony Muslin
- Antikainen R.
- Antonell A.
- Antti Karlsson
- Antti Palomäki
- Anttonen V.
- Antúnez C.
- Anu Jalanko
- Anu Loukola
- Aoibhinn Lynch
- Aparicio H. J.
- Aparna Chhibber
- Apinya Lertratanakul
- Apostolova L. G.
- Appollonio I.
- Arcaro M.
- Archetti S.
- Arjun Masurkar
- Armstrong N.
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- Arto Lehisto
- Arto Lehistö
- Arto Mannermaa
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- Elina Järvensivu
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- Elizabeth A Crocco
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- Yeunjoo E Song
- Yi Zhao
- Ying Wu
- Yoav Ben-Shlomo
- Yogen Patel
- Younkin S. G.
- Yu C. -E.
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- Yuanchao Zhang
- Yuk Yee Leung
- Yunfeng Huang
- Yunju Yang
- Zare H.
- Zdenka Pausova
- Zhang X.
- Zhang Y.
- Zhao Y.
- Zhao Y.
- Zhou W.
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- Ziemann A.
- Zoia C. P.
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- Zulaica M.
- Zulma Sevillano
- Álvarez V.
- Åsa Hedman
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2022
- Field of study
Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele
New insights into the genetic etiology of Alzheimer’s disease and related dementias
- Author
- Aaltonen Lauri
- Aaltonen Vesa
- Aarsland Dag
- Aavikko Mervi
- Abalos Mariana Sanchez
- Abdelnour Carla
- Abner Erin
- Abraham Richard
- Adams Hieab
- Adams Perrie M.
- Adarmes-Gómez Ad
- Adarmes-Gómez Astrid D.
- Aguilera Nuria
- Aguilera Nuria
- Aguirre Alyssa
- Ahmad Shahzad
- Akinyemi Rufus O.
- Al-Chalabi Ammar
- Alarcón-Martín Emilio
- Albert Marilyn S.
- Albin Roger L.
- Alcolea Daniel
- Alegret Montserrat
- Ali Muhammad
- Allen Mariet
- Allende Irene Rosas
- Alonso María Dolores
- Alonso María Dolores
- Alvarez Ignacio
- Alvarez Lisa
- Amer-Ferrer Guillermo
- Amin Najaf
- Amouyel Philippe
- Anastasiou Anna
- Anastasiou Costas
- Andrade Victor
- Andreassen Ole A.
- Andreoni Simona
- Antequera Martirio
- Antikainen Riitta
- Antonell Anna
- Anttonen Vuokko
- Antúnez Carmen
- Aparicio Hugo J.
- Apostolova Liana G.
- Appollonio Ildebrando
- Arcaro Marina
- Archetti Silvana
- Armstrong Nicola
- Armstrong Nicola J.
- Arnold Steven E.
- Arosio Beatrice
- Arvas Mikko
- Assogna Francesca
- Asthana Sanjay
- Athanasiu Lavinia
- Atwood Craig S.
- Auge Franck
- Auranen Annika
- Auvinen Päivi
- Awaisa Ghazal
- Ayres Gayle
- Bacha Juan Ignacio
- Bahadori Maryam
- Bahrami Shahram
- Bailly Henri
- Baldwin Clinton T.
- Banaj Nerisa
- Baquero Miquel
- Barber Robert C.
- Barnes Lisa L.
- Barral Sandra
- Barral Sandra
- Bass Nicholas J.
- Bass Nick
- Bastiani Patrizia
- Bayer Anthony
- Beach Thomas G.
- Becker James T.
- Becker James T.
- Becker Tim
- Beecham Gary W.
- Beekly Duane
- Behrens Tim
- Beiser Alexa
- Belezhanska Diyana
- Bellenguez Céline
- Below Jennifer E.
- Below Jennifer E.
- Ben-Shlomo Yoav
- Benchek Penelope
- Benchek Penelope
- Benitez Bruno A.
- Bennett David
- Benussi Alberto
- Benussi Luisa
- Bergh Sverre
- Bernardo-Harrington Mateus
- Berr Claudine
- Bertelson John
- Besse Céline
- Bessi Valentina
- Betts Jo
- Bhangale Tushar
- Biessels Geert Jan
- Binetti Giuliano
- Bing Nan
- Bird Thomas D.
- Bis Joshua C.
- Biswas Shameek
- Bizarro Alessandra
- Bjerke Maria
- Blacker Deborah
- Blesa Rafael
- Blomster Timo
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- Boeve Bradley F.
- Boland Anne
- Borroni Barbara
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- Bossù Paola
- Bowen James D.
- Bowers Natalie
- Boxer Adam
- Brauer Matt
- Brayne Carol
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- Bressler Jan
- Breteler Monique
- Brewer James
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- Brodaty Henry
- Broeckhoven Christine Van
- Bronson Paola
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- Chasman Daniel
- Chasse Scott
- Chatelain Clement
- Chauhan Ganesh
- Chen Chia-Yen
- Chen Hao
- Chen Hubert
- Chen Hung-Hsin
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- Chene Geneviève
- Chesi Alessandra
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- Chillotti Caterina
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- Close David
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- Comic Hata
- Conti Elisa
- Cores Valeria
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- Costa Marcos R.
- Costantini Emanuele
- Cox Simon
- Craft Suzanne
- Craig David
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- Cuccaro Michael L.
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- Cuesta Carolina
- Cullum Munro
- Cummings Beryl
- Cupples Adrienne L.
- Custodero Carlo
- Daian Delphine
- Dalmasso Maria Carolina
- Daly Mark
- Damotte Vincent
- Daniele Antonio
- Darby Eveleen
- Dardiotis Efthimios
- Dartigues Jean-François
- Davies Chloe
- Davies Gail
- Davis Barbara
- Davis Justin Wade
- de Deyn Peter Paul
- De Jager Philip L.
- de Mendonça Alexandre
- de Munain Adolfo Lopez
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- Debette Stéphanie
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- Deckert Jürgen
- del Ser Teodoro
- Deleuze Jean-François
- della Briotta Parola Pietro
- della Briotta Parolo Pietro
- Deloukas Panagiotis
- Deloukas Pangiotis
- Denning Nicola
- Deramecourt Vincent
- Deramerourt Vincent
- DeStefano Anita
- DeToledo John
- Dichgans Martin
- Dick Malcolm
- Dickson Dennis W.
- Diego Susana
- Diehl-Schmid Janine
- Diez-Fairen Mónica
- Diogo Dorothee
- Djurovic Srdjan
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- Donner Kati
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- Dowzell Kimberley
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- Dupuis Josée
- Duron Emmanuelle
- Düzel Emrah
- Eaton Susan
- Ehm Meg
- Eicher John
- Eiriksdottir Gudny
- Eklund Kari
- Elenius Klaus
- Elliott Amanda
- Engelborghs Sebastiaan
- Epelbaum Jacques
- Ertekin-Taner Nilüfer
- Escott-Price Valentina
- Escuela R.
- Escuela Rocío
- Esmaeeli Sahar
- Espinosa Ana
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- Ferreira Catarina B.
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- Ferris Steven
- Feulner Thomas
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- Frölich Lutz
- Fulton-Howard Brian
- Fulton-Howard Brian
- Färkkilä Martti
- Gailhajenet Anna
- Galasko Douglas R.
- Galeano Pablo
- Galimberti Daniela
- Gamboa Adriana
- Ganguli Mary
- Ganna Andrea
- Garcia-Gonzalez Pablo
- Garcia-Madrona Sebastian
- Garcia-Ribas Guillermo
- Garcia-Tabuenca Javier
- García-Alberca Jose Maria
- García-González Pablo
- Garrote-Espina L.
- Garrote-Espina Lorena
- Gearing Marla
- Geerlings Mirjam
- Georgantas Bob
- George-Hyslop Peter St
- Germani Sandra
- Gerrish Amy
- Geschwind Daniel H.
- Ghanbari Mohsen
- Ghetti Bernardino
- Ghidoni Roberta
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- Gonzalez Hector M.
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- Gordillo Jorge Esparza
- Gormley Padhraig
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- van der Flier Wiesje M.
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- van der Lugt Aad
- van Duijn Cornelia M.
- van Eldik Linda J.
- van Lent Debora Melo
- van Rooij Jeroen
- van Swieten John
- Vance Jeffery
- Vandenberghe Rik
- Vardarajan Badri N.
- Vardy Emma
- Vargas Liliana
- Vassar Robert
- Verhey Frans
- Vicente Maria Pilar
- Vidal Jean-Sébastien
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- Vigo-Ortega Rosario
- Vilas Raquel Huerto
- Vinters Harry V.
- Virolainen Petri
- Vivancos Liliana
- Vogelgsang Jonathan
- Vojinovic Dina
- Vonsattel Jean-Paul
- Voutilainen Markku
- Vyhnalek Martin
- Wadhawan Samir
- Wagner Michael
- Wallon David
- Wang Clarence
- Wang Li-San
- Wang Ruiqi
- Wang Yanbing
- Warden Donald
- Waring Jeff
- Waring Jeffrey
- Warner Nick
- Warren Jason D.
- Waterworth Dawn
- Weber Heike
- Weinhold Leonie
- Weinstein Galit
- Weintraub Sandra
- Welsh-Bohmer Kathleen A.
- Whelan Christopher
- Whitehead Patrice L.
- Wichmann H-Erich
- Wigmore Eleonor
- Wijsman Ellen M.
- Wilcock Gordon
- Wilhelmsen Kirk C.
- Williams Amy
- Williams Benjamin
- Williams Dylan
- Williams Julie
- Williamson Jennifer
- Wilms Henrik
- Wiltfang Jens
- Windle Gill
- Wingo Thomas S.
- Wisniewski Thomas
- Wittfeld Katharina
- Woltjer Randall L.
- Wong Regis
- Woods Bob
- Woon Martin
- Wright Clinton B.
- Wu Chuang-Kuo
- Wu Ying
- Xia Tai-he
- Xu Ethan
- Xu Fanli
- Yanek Lisa
- Yang Qiong
- Yang Yunju
- Yannakoulia Mary
- Yaqub Amber
- Younkin Steven G.
- Yu Chang-En
- Yu Lei
- Zare Habil
- Zhang Xiaoling
- Zhang Yuanchao
- Zhao Yi
- Zhao Yi
- Zhou Wei
- Zhu Congcong
- Zhu Xiongwei
- Ziemann Adam
- Zoia Chiara Paola
- Zompo Maria Del
- Zulaica Miren
- Álvarez Victoria
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/04/2022
- Field of study
Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele