67 research outputs found
Collective renewable energy prosumers and the promises of the energy union: Taking stock
A key strategy in the European Union’s ambition to establish an ‘Energy Union’ that is not just clean, but also fair, consists of empowering citizens to actively interact with the energy market as self-consumers or prosumers. Although renewable energy sources (RES) prosumerism has been growing for at least a decade, two new EU directives are intended to legitimise and facilitate its expansion. However, little is known about the full range of prosumers against which to measure policy effectiveness. We carried out a documentary study and an online survey in nine EU countries to shed light on the demographics, use of technology, organisation, financing, and motivation as well as perceived hindering and facilitating factors for collective prosumers. We identified several internal and external obstacles to the successful mainstreaming of RES prosumerism, among them a mismatch of policies with the needs of different RES prosumer types, potential organisational weaknesses as well as slow progress in essential reforms such as decentralising energy infrastructures. Our baseline results offer recommendations for the transposition of EU directives into national legislations and suggest avenues for future research in the fields of social, governance, policy, technology, and business models
Atlas de las flotas de pesca españolas de aguas europeas atlánticas
The European Commission has acknowledged the value of fleet-based management approaches since the 2001
Green Paper on the Common Fisheries Policy (CFP). In the 2009 Green Paper, this was again recognized as a
key area of interest for future development of the CFP, in particular setting the technical basis for the recent
Data Collection Framework (DCF), which specifies the standard for national fishery sampling programs within a
pan-European context. These policy changes require deeper and up to date knowledge about European fleets
and fisheries, thus encouraging Member States to undertake scientific projects in order to obtain appropriate
fleet segmentations classifying their fishing activities within a hierarchical structure.
The work presented in this book is the first comprehensive analysis of the Spanish fleets operating in Atlantic
European waters, taking into account both European and national management requirements. This has been
possible due to the availability of official logbooks, which provide the broadest perspective on the activity of
Spanish fleets in the study area. The only exception to this is small scale fisheries, pursued mainly by vessels of
less than 10 m of length and, therefore, not subject to the requirement of keeping logbooks.
In order to match better European and Spanish fleet classifications, a new level (“Management Unit”) is
proposed here, which is placed between “modalidad”, used in the Spanish regulations, and “métier”, as is
defined by the recent DCF.
Spanish national waters comprise four fishing grounds, two of which are in the European Atlantic. Nine
Management Units have been identified in the Northern Spanish fishing ground: bottom otter trawl (OTB10),
bottom pair trawl (PTB10), purse seine (PSN10), set long line (LLS10), set gillnet targeting hake (GNS11), set
gillnet targeting anglerfish (GNS12), trolling (LTL11) and bait-boats (LHP11) targeting albacore, and hand line
targeting mackerel (LHP12). Two Management Units have been identified in Southern Spanish waters: bottom
otter trawl (OTB20) and purse seine (PSN20).
In European waters outside Spain, six Management Units have been identified in non-Iberian waters: bottom
otter trawl (OTB50), bottom pair trawl (PTB50), set long line (LLS50) and set gillnet (GNS50) by vessels of
more than 100 GRT, and set long line (LLS60) and set gillnet (GNS60) by vessels of less than 100 GRT. Finally,
one Management Unit using bottom otter trawl has been found to operate in Portuguese waters (OTB70).
Unluckily, the analyses made on the logbooks of the Spanish fleet using drifting long line could not be used to
categorize this fleet due to the geographical limitations of the logbooks available.
After detailed analyses and categorization of the Management Units, the results obtained were used in an
exercise to test the usefulness and feasibility of using logbook information to answer some DCF requirements.
This revealed that logbooks are an essential tool to deal with bioeconomic challenges posed by the new CFP.Versión del edito
Association of a single nucleotide polymorphism combination pattern of the Klotho gene with non-cardiovascular death in patients with chronic kidney disease
Chronic kidney disease (CKD) is associated with an elevated risk of all-cause mortality, with cardiovascular death being extensively investigated. However, non-cardiovascular mortality represents the biggest percentage, showing an evident increase in recent years. Klotho is a gene highly expressed in the kidney, with a clear influence on lifespan. Low levels of Klotho have been linked to CKD progression and adverse outcomes. Single nucleotide polymorphisms (SNPs) of the Klotho gene have been associated with several diseases, but studies investigating the association of Klotho SNPs with noncardiovascular death in CKD populations are lacking. The main aim of this study was to assess whether 11 Klotho SNPs were associated with non-cardiovascular death in a subpopulation of the National Observatory of Atherosclerosis in Nephrology (NEFRONA) study (n ¼ 2185 CKD patients). After 48 months of follow-up, 62 cardiovascular deaths and 108 non-cardiovascular deaths were recorded. We identified a high non-cardiovascular death risk combination of SNPs corresponding to individuals carrying the most frequent allele (G) at rs562020, the rare allele (C) at rs2283368 and homozygotes for the rare allele (G) at rs2320762 (rs562020 GG/AG þ rs2283368 CC/CT þ rs2320762 GG). Among the patients with the three SNPs genotyped (n ¼ 1016), 75 (7.4%) showed this combination. Furthermore, 95 (9.3%) patients showed a low-risk combination carrying all the opposite genotypes (rs562020 AA þ rs2283368 TT þ rs2320762 GT/TT). All the other combinations [n ¼ 846 (83.3%)] were considered as normal risk. Using competing risk regression analysis, we confirmed that the proposed combinations are independently associated with a higher fhazard ratio [HR] 3.28 [confidence interval (CI) 1.51-7.12]g and lower [HR 6 × 10- (95% CI 3.3 × 10--1.1 × 10-)] risk of suffering a non-cardiovascular death in the CKD population of the NEFRONA cohort compared with patients with the normal-risk combination. Determination of three SNPs of the Klotho gene could help in the prediction of non-cardiovascular death in CKD
Association of candidate gene polymorphisms with chronic kidney disease : Results of a case-control analysis in the NEFRONA cohort
Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2,445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionization-time of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD
Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality
Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies
Background Genome-wide association studies (GWAS) in Parkinson's disease have increased the scope of biological knowledge about the disease over the past decade. We aimed to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into the causes of Parkinson's disease. Methods We did a meta-analysis of 17 datasets from Parkinson's disease GWAS available from European ancestry samples to nominate novel loci for disease risk. These datasets incorporated all available data. We then used these data to estimate heritable risk and develop predictive models of this heritability. We also used large gene expression and methylation resources to examine possible functional consequences as well as tissue, cell type, and biological pathway enrichments for the identified risk factors. Additionally, we examined shared genetic risk between Parkinson's disease and other phenotypes of interest via genetic correlations followed by Mendelian randomisation. Findings Between Oct 1, 2017, and Aug 9, 2018, we analysed 7·8 million single nucleotide polymorphisms in 37 688 cases, 18 618 UK Biobank proxy-cases (ie, individuals who do not have Parkinson's disease but have a first degree relative that does), and 1·4 million controls. We identified 90 independent genome-wide significant risk signals across 78 genomic regions, including 38 novel independent risk signals in 37 loci. These 90 variants explained 16–36% of the heritable risk of Parkinson's disease depending on prevalence. Integrating methylation and expression data within a Mendelian randomisation framework identified putatively associated genes at 70 risk signals underlying GWAS loci for follow-up functional studies. Tissue-specific expression enrichment analyses suggested Parkinson's disease loci were heavily brain-enriched, with specific neuronal cell types being implicated from single cell data. We found significant genetic correlations with brain volumes (false discovery rate-adjusted p=0·0035 for intracranial volume, p=0·024 for putamen volume), smoking status (p=0·024), and educational attainment (p=0·038). Mendelian randomisation between cognitive performance and Parkinson's disease risk showed a robust association (p=8·00 × 10−7). Interpretation These data provide the most comprehensive survey of genetic risk within Parkinson's disease to date, to the best of our knowledge, by revealing many additional Parkinson's disease risk loci, providing a biological context for these risk factors, and showing that a considerable genetic component of this disease remains unidentified. These associations derived from European ancestry datasets will need to be followed-up with more diverse data. Funding The National Institute on Aging at the National Institutes of Health (USA), The Michael J Fox Foundation, and The Parkinson's Foundation (see appendix for full list of funding sources)
I Congresso Ibero-Americano de Bibliotecas Escolares
Actas de la primera edición del I Congreso Iberoamericano de Bibliotecas Escolares, CIBES 2015, organizado por la Universidad Carlos III de Madrid (España), la Universidad Estatal Paulista (Brasil) y el Ayuntamiento de Getafe (España). Celebrado: 21 - 23 de octubre de 2015 en la Universidad Estatal Paulista (Marília) y 26 - 28 de octubre de 2015 en la Universidad Carlos III de Madrid (Getafe)Universidad Carlos III de Madrid (España)Universidad Estatal Paulista (Brasil)Ayuntamiento de Getafe (España)Dimensiones y visiones de la biblioteca escolar en una Educación por competencias: la
necesidad de una política estratégica / Miguel Ángel Marzal. -- Getafe ciudad educadora,
lectora y escritora: Bibliotecas escolares / Lourdes Muñoz Santiuste. -- Presente y
futuro: biblioteca escolar-CREA y proyectos interdisciplinares / Rosa Piquín. -- Cultura
en información: un reto esencial de la biblioteca escolar / Mónica Baró. -- Bibliotecas
escolares de Galicia: un mundo de oportunidades a favor de la Educación / Cristina Novoa.
-- 10 años de la Red de Bibliotecas Escolares de Extremadura (REBEX) / Casildo Macías
Pereira. -- Biblioteca Escolar y uso ético de la información para una Cultura de Paz / Ana
Barrero Tíscar. -- Dinamización de la Biblioteca Escolar Plumita durante el curso escolar
2014/15 / María Antonia Cano Cañada. -- Experiencia de la creación de una biblioteca
escolar / Susana Santos Martín. -- Grupo cooperativo Bibliotecas escolares en Red-Albacete
/ José Manuel Garrido Argandoña y Eva Leal Scasso. -- La BCREA "Juan Leiva". El fomento de
la lectura desde la web social / Andrés Pulido Villar. -- Proceso de implantación de una
herramienta de autoevaluación en la red de bibliotecas escolares de Extremadura (REBEX) /
Casildo Macías Pereira. -- La biblioteca escolar: abriendo fronteras / Lorena Verónica
Cabrera Orellana. -- O programa RBE e a avaliaçao das bibliotecas escolares: melhoria,
desenvolvimiento e innovaçao / Elsa Conde. -- Profesional de Biblioteconomía y
Documentación: esencial en la plantilla de la escuela / Pilar del Campo Puerta. -- Una
mirada activa al proceso educativo desde la biblioteca escolar / María Jesús Fontela
Fernández . -- Con otra mirada "La ilustración como vehículo de comunicación y aprendizaje
en las bibliotecas escolares" / Pablo Jurado Sánchez-Galán. -- Fingertips. Recriar a
biblioteca escolar na sala de aula / Rui Alfonso Mateus. -- Hablemos de libros. Cómo
transformar una clase de literatura en una comunidad de interpretación de textos /
Francisco César Díaz Rey. -- Inclusión social de familias inmigrantes a través de un
programa de aprendizaje de la lengua castellana / Ana Carmen Tolino Fernández-Henarejos.
-- O desenvolvimento de atividades de mediação de leitura em biblioteca escolar: o caso da
biblioteca da Escola Sesc de Ensino Médio / Vagner Amaro. -- La biblioteca escolar.
Proceso de enseñanza-aprendizaje de padres a hijos / Ana Carmen Tolino Fernández-
Henarejos. -- Leo con y para los demás / Ismael Fernández Fernández, Ana María Moreno
Vicente y Ana Beatriz Vicente Pérez. -- Nanas y arrullo. Poesía a la deriva / Bernardo
Fuentes Navarrete y Carlos García-Romeral Pérez. -- Gestión y evaluación de servicios
bibliotecarios para personas con dislexia: una biblioteca escolar inclusiva desde una
perspectiva internacional / Carmen Jorge García-Reyes. -- Sueños lectores compartidos
hechos realidad: la biblioteca escolar del C.E.I.P-S.E.S-A.A “LA PAZ” de Albacete / Ana
Rosa Cabañero Tobarra, Juan Manuel Herráez, Eva Leal Scasso, María Marín Sánchez, Ana
Belén Medrano Martínez y María José Nortes Ruipérez. -- El programa biblioteca escuela en
Civican. La literatura como elemento motivador para la alfabetización informacional /
Villar Arellano Yanguas. -- La competencia digital en el diseño curricular: desde la
biblioteca al aula / Felicidad Campal García. -- O deselvomimento da pesquisa escolar por
meio da competência em informaçao / Luciane de Fátima Cavalcante Beckman y Marta Leandro
da Mata. -- Proyecto escolar de investigación documental "Te pillé leyendo" / José Manuel
Garrido Argandoña. -- Aprender com a Biblioteca Escolar: formar para as literacias / Paula
Correia y Isabel Mendinhos. -- Sucedió en el siglo XX / María Antonia Becerra Montalbán,
Ángel Bernabé Muñoz y Sofía Vaz Romero. -- El Club de lectura en la nube / Belén Benito
Blázquez y Ana Ordás García. -- Promover a leitura e a escrita na era digital:
prácticas nas bibliotecas escolares / María Raquel Ramos. -- A biblioteca escolar e o
desafío da interculturalidade: o projeto Ser + cidadao / María da Conceição Tomé. --
Cuando la competencia digital encontró a la alfabetización informacional o Mucho ruido y
pocas nueces / Felicidad Campal García. -- Hora de ler, un programa para el fomento de la
lectura en contexto educativo / Cristina Novoa. -- Hábitos de lectura para las
competencias en información y alfabetización en información en bibliotecas escolares de
Puerto Rico / Karen Denise Centeno Casillas. -- Repositorios digitales en las bibliotecas
escolares andaluzas: situación, modelos y herramientas para su creación / Dolores Olmos
Olmos y Andrés Pulido Villar. -- Trabajando las competencias clave con las aventuras de
Mozarito en Extremadura / María Teresa Carballosa González y María Esther Nieto Vidal. --
Análisis de modelos de evaluación de la web de la biblioteca escolar / Raúl Cremades
García. -- Emociónate con las historias: El bosque de las emociones e historias con mucho
teatro / Esther Luis Pérez y Ana María Peromingo Fernández. -- Biblioteca escolar de
innovación y continuación / E. María Guerrero Palacios y Silvia Mora Ramírez. -- Uso de
estándares y licencias para la creación y difusión de contenidos en las bibliotecas
escolares / José Luis Barreiro Cebey. -- La biblioteca escolar digital móvil / Javier
Fernández Delgado. -- Uso de aplicaciones móviles para el desarrollo de
la competencia lingüística. Proyecto Hansel App Gretel / Dolores Olmos Olmos. -- A memória
e a mediação segundo Vigotski / Leda Maria Araújo, Patricia Celia Santana, Sueli Bortolin
y Leticia Gorri Molina. -- Bibliotecas escolares como tema de estudo dos alunos de
graduação em blioteconomia do Instituto de Ensino Superior da FUNLEC: estado da arte /
Tiago Pereira Nocera y Rodrigo Pereira. -- Ações de mediação da leitura e da informação
em bibliotecas escolares: um olhar sobre as bibliotecas dos Colégios de Aplicação /
Tatyanne Christina Gonçalves Ferreira Valdez y Alberto Calil Júnior. -- Mediação
pedagógica numa biblioteca de escola pública em Londrina / Rovilson José da Silva, Teba
Silva Yllana y Sueli Bortolin. -- Utilização de categorias por cores em sistema de
biblioteca voltado ao público infanto-juvenil / Liliana Giusti Serra. -- Atividades de
ensino dos atos de leitura com crianças em risco social / Adriana Naomi Fukushima da Silva
y Dagoberto Buim Arena. -- Biblioteca escolar: espaço de significados entre
alunos, professores e bibliotecários / Rodrigo Barbosa Paulo, Marisa Xavier, Helen Castro
Casarin y Creuza Barbaroto. -- A Biblioteca Escolar no Contexto da Legislação e
do Processo Educativo / Eliane Lourdes da Silva Moro, Francisca Rosaline Leite Mota y
Raimundo Martins de Lima. -- O jornal impresso como fonte de informação: a importância da
formação de leitores críticos / Mariana Pícaro Cerigatto. -- Bibliotecas escolares no
estado do Rio Grande do Sul: a trajetória de realização dos fóruns gaúchos pela melhoria
das bibliotecas escolares / Eliane Lourdes da Silva Moro y Lizandra Brasil Estabel. -- O
acesso à informação dos usuários surdos na biblioteca escolar / André Luís Onório
Coneglian y Mayara Melo Santana. -- Aprendizagem coletiva de bibliotecários e a
competência de pesquisa dos docentes: o caso do Instituto Federal do Espírito Santo /
Maristela Almeida Mercandeli Rodrigues y Beatriz Quiroz Villardi. -- Biblioteca escolar:
atores, parâmetros e competências / Mavi Galante Mancera Dall´Acqua Carvalho y Claudio
Marcondes de Castro Filho. -- Estratégias de aprendizagem de escrita no
Ensino Fundamental II / Érika Christina Kohle. -- Bebês e livros: leitura nas bebetecas.
Kenia Adriana de Aquino Modesto Silva, Juliane Francischeti Martins Motoyama y Renata
Junqueira de Souza. -- Práticas alternativas para organização de acervos nos espaços de
leitura em ambientes escolares / Luciana Souza Gracioso, Ariovaldo Alves,
Débora Nascimento, Suelen Redondo, Tainara Torika Kiri de Castro, Elizabete Angelon y
Eduardo Barbosa. -- Reflexões sobre a modelagem e criação de uma Rede Virtual de Leitores
para Bibliotecas Escolares / Carla Floriana Martins y Raoni Guerra Rajão. -- Biblioteca
escolar: espaço de formação leitora? / Silvana Ferreira de Souza Balsan y Renata
Junqueira de Souza. -- “Se a Biblioteca Escolar é minha mãe, o Google é meu pai”:
representações da relação entre Biblioteca Escolar e Google no imaginário de
alunos do ensino técnico / Adriana Bogliolo Sirihal-Duarte, Maria L. Amorim Antunes y
Raquel Miranda Vilela Paiva. -- Desafios e propostas para a universalização das
bibliotecas escolares no Brasil e na Espanha / Rodrigo Pereira, Daniela Spudeit y Fernanda
de Sales. -- Bibliotecário educador: possibilidades de atuação no contexto da biblioteca
escolar / André Carlos da Silva, Valéria Martin Valls y Mariana de Paula Silva. -- Uma ONG
para Bibliotecas Escolares : estratégia para ampliar a igualdade e capacidade de acesso
e uso da informação e educação escolar de qualidade / Suelen Camilo Ferreira y Luciana de
Souza Gracioso. -- O aluno com deficência: o papel do bibliotecário na disponibilidade de
recursos acessíveis na biblioteca escolar / Adriano de Sales Coelho, Rosilene de Melo
Oliveira y Marcos Pastana Santos. -- Biblioteca digital virtual e o uso do tablete: uma
possibilidade de construção de novas práticas de leitura na escola / Barbara Cibelli da
Silva Monteagudo y Dagoberto Buim Arena. -- A importância da biblioteca na educação de
crianças de 0 a 3 anos / Yngrid Karolline Mendonça Costa y Cyntia Graziella Guizelim
Simões Girotto. -- Comportamento Informacional de adolescentes: a relação com bibliotecas
e escolas / Nelson Sebastian Silva-Jerez y Helen de Castro S. Casarin
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Identification of candidate Parkinson disease genes by integrating genome-wide association study, expression, and epigenetic data sets
Importance Substantial genome-wide association study (GWAS) work in Parkinson disease (PD) has led to the discovery of an increasing number of loci shown reliably to be associated with increased risk of disease. Improved understanding of the underlying genes and mechanisms at these loci will be key to understanding the pathogenesis of PD.
Objective To investigate what genes and genomic processes underlie the risk of sporadic PD.
Design and Setting This genetic association study used the bioinformatic tools Coloc and transcriptome-wide association study (TWAS) to integrate PD case-control GWAS data published in 2017 with expression data (from Braineac, the Genotype-Tissue Expression [GTEx], and CommonMind) and methylation data (derived from UK Parkinson brain samples) to uncover putative gene expression and splicing mechanisms associated with PD GWAS signals. Candidate genes were further characterized using cell-type specificity, weighted gene coexpression networks, and weighted protein-protein interaction networks.
Main Outcomes and Measures It was hypothesized a priori that some genes underlying PD loci would alter PD risk through changes to expression, splicing, or methylation. Candidate genes are presented whose change in expression, splicing, or methylation are associated with risk of PD as well as the functional pathways and cell types in which these genes have an important role.
Results Gene-level analysis of expression revealed 5 genes (WDR6 [OMIM 606031], CD38 [OMIM 107270], GPNMB [OMIM 604368], RAB29 [OMIM 603949], and TMEM163 [OMIM 618978]) that replicated using both Coloc and TWAS analyses in both the GTEx and Braineac expression data sets. A further 6 genes (ZRANB3 [OMIM 615655], PCGF3 [OMIM 617543], NEK1 [OMIM 604588], NUPL2 [NCBI 11097], GALC [OMIM 606890], and CTSB [OMIM 116810]) showed evidence of disease-associated splicing effects. Cell-type specificity analysis revealed that gene expression was overall more prevalent in glial cell types compared with neurons. The weighted gene coexpression performed on the GTEx data set showed that NUPL2 is a key gene in 3 modules implicated in catabolic processes associated with protein ubiquitination and in the ubiquitin-dependent protein catabolic process in the nucleus accumbens, caudate, and putamen. TMEM163 and ZRANB3 were both important in modules in the frontal cortex and caudate, respectively, indicating regulation of signaling and cell communication. Protein interactor analysis and simulations using random networks demonstrated that the candidate genes interact significantly more with known mendelian PD and parkinsonism proteins than would be expected by chance.
Conclusions and Relevance Together, these results suggest that several candidate genes and pathways are associated with the findings observed in PD GWAS studies
Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes
Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues
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