Shared polygenic risk and causal inferences in amyotrophic lateral sclerosis

Autor: Bandres‐Ciga, S, Noyce, AJ, Hemani, G, Nicolas, A, Calvo, A, Mora, G, Arosio, A, Barberis, M, Bartolomei, I, Battistini, S, Benigni, M, Borghero, G, Brunetti, M, Cammarosano, S, Cannas, A, Canosa, A, Capasso, M, Caponnetto, C, Caredda, C, Carrera, P, Casale, F, Cavallaro, S, Chiò, A, Colletti, T, Conforti, FL, Conte, A, Corrado, L, Costantino, E, D'Alfonso, S, Fasano, A, Femiano, C, Ferrarese, C, Fini, N, Floris, G, Fuda, G, Giannini, F, Grassano, M, Ilardi, A, La Bella, V, Lattante, S, Logroscino, G, Logullo, FO, Loi, D, Lunetta, C, Mancardi, G, Mandich, P, Mandrioli, J, Manera, U, Marangi, G, Marinou, K, Marrali, G, Marrosu, MG, Mazzini, L, Melis, M, Messina, S, Moglia, C, Monsurro, MR, Mosca, L, Occhineri, P, Origone, P, Pani, C, Penco, S, Petrucci, A, Piccirillo, G, Pirisi, A, Pisano, F, Pugliatti, M, Restagno, G, Ricci, C, Rita Murru, M, Riva, N, Sabatelli, M, Salvi, F, Santarelli, M, Sideri, R, Simone, I, Spataro, R, Tanel, R, Tedeschi, G, Tranquilli, S, Tremolizzo, L, Trojsi, F, Volanti, P, Zollino, M, Abramzon, Y, Arepalli, S, Baloh, RH, Bowser, R, Brady, CB, Brice, A, Broach, J, Campbell, RH, Camu, W, Chia, R, Cooper‐Knock, J, Cusi, D, Ding, J, Drepper, C, Drory, VE, Dunckley, TL, Eicher, JD, Faghri, F, Feldman, E, Kay Floeter, M, Fratta, P, Geiger, JT, Gerhard, G, Gibbs, JR, Gibson, SB, Glass, JD, Hardy, J, Harms, MB, Heiman‐Patterson, TD, Hernandez, DG, Jansson, L, Kamel, F, Kirby, J, Kowall, NW, Laaksovirta, H, Landi, F, Le Ber, I, Lumbroso, S, MacGowan, DJL, Maragakis, NJ, Mouzat, K, Murphy, NA, Myllykangas, L, Nalls, MA, Orrell, RW, Ostrow, LW, Pamphlett, R, Pickering‐Brown, S, Pioro, E, Pliner, HA, Pulst, SM, Ravits, JM, Renton, AE, Rivera, A, Robbrecht, W, Rogaeva, E, Rollinson, S, Rothstein, JD, Salvi, E, Scholz, SW, Sendtner, M, Shaw, PJ, Sidle, KC, Simmons, Z, Singleton, AB, Stone, DC, Sulkava, R, Tienari, PJ, Traynor, BJ, Trojanowski, JQ, Troncoso, JC, Van Damme, P, Van Deerlin, VM, Van Den Bosch, L, Zinman, L, Stone, DJ
Přispěvatelé: Bandres-Ciga, Sara, Noyce, Alastair J., Hemani, Gibran, Nicolas, Aude, Calvo, Andrea, Mora, Gabriele, Arosio, Alessandro, Barberis, Marco, Bartolomei, Ilaria, Battistini, Stefania, Benigni, Michele, Borghero, Giuseppe, Brunetti, Maura, Cammarosano, Stefania, Cannas, Antonino, Canosa, Antonio, Capasso, Margherita, Caponnetto, Claudia, Caredda, Carla, Carrera, Paola, Casale, Federico, Cavallaro, Sebastiano, Chiò, Adriano, Colletti, Tiziana, Conforti, Francesca L., Conte, Amelia, Corrado, Lucia, Costantino, Emanuela, D'Alfonso, Sandra, Fasano, Antonio, Femiano, Cinzia, Ferrarese, Carlo, Fini, Nicola, Floris, Gianluca, Fuda, Giuseppe, Giannini, Fabio, Grassano, Maurizio, Ilardi, Antonio, La Bella, Vincenzo, Lattante, Serena, Logroscino, Giancarlo, Logullo, Francesco O., Loi, Daniela, Lunetta, Christian, Mancardi, Gianluigi, Mandich, Paola, Mandrioli, Jessica, Manera, Umberto, Marangi, Giuseppe, Marinou, Kalliopi, Marrali, Giuseppe, Marrosu, Maria Giovanna, Mazzini, Letizia, Melis, Maurizio, Messina, Sonia, Moglia, Cristina, Monsurro, Maria Rosaria, Mosca, Lorena, Occhineri, Patrizia, Origone, Paola, Pani, Carla, Penco, Silvana, Petrucci, Antonio, Piccirillo, Giovanni, Pirisi, Angelo, Pisano, Fabrizio, Pugliatti, Maura, Restagno, Gabriella, Ricci, Claudia, Rita Murru, Maria, Riva, Nilo, Sabatelli, Mario, Salvi, Fabrizio, Santarelli, Marialuisa, Sideri, Riccardo, Simone, Isabella, Spataro, Rossella, Tanel, Raffaella, Tedeschi, Gioacchino, Tranquilli, Stefania, Tremolizzo, Lucio, Trojsi, Francesca, Volanti, Paolo, Zollino, Marcella, Abramzon, Yevgeniya, Arepalli, Sampath, Baloh, Robert H., Bowser, Robert, Brady, Christopher B., Brice, Alexi, Broach, Jame, Campbell, Roy H., Camu, William, Chia, Ruth, Cooper-Knock, John, Cusi, Daniele, Ding, Jinhui, Drepper, Carsten, Drory, Vivian E., Dunckley, Travis L., Eicher, John D., Faghri, Faraz, Feldman, Eva, Kay Floeter, Mary, Fratta, Pietro, Geiger, Joshua T., Gerhard, Glenn, Gibbs, J. Raphael, Gibson, Summer B., Glass, Jonathan D., Hardy, John, Harms, Matthew B., Heiman-Patterson, Terry D., Hernandez, Dena G., Jansson, Lilja, Kamel, Freya, Kirby, Janine, Kowall, Neil W., Laaksovirta, Hannu, Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, Macgowan, Daniel J. L., Maragakis, Nicholas J., Mouzat, Kevin, Murphy, Natalie A., Myllykangas, Liisa, Nalls, Mike A., Orrell, Richard W., Ostrow, Lyle W., Pamphlett, Roger, Pickering-Brown, Stuart, Pioro, Erik, Pliner, Hannah A., Pulst, Stefan M., Ravits, John M., Renton, Alan E., Rivera, Alberto, Robbrecht, Wim, Rogaeva, Ekaterina, Rollinson, Sara, Rothstein, Jeffrey D., Salvi, Erika, Scholz, Sonja W., Sendtner, Michael, Shaw, Pamela J., Sidle, Katie C., Simmons, Zachary, Singleton, Andrew B., Stone, David C., Sulkava, Raimo, Tienari, Pentti J., Traynor, Bryan J., Trojanowski, John Q., Troncoso, Juan C., Van Damme, Philip, Van Deerlin, Vivianna M., Van Den Bosch, Ludo, Zinman, Lorne, Stone, David J., Van Damme, P, Bandres-Ciga, S, Noyce, A, Hemani, G, Nicolas, A, Calvo, A, Mora, G, Tienari, P, Stone, D, Nalls, M, Singleton, A, Chiò, A, Traynor, Bryan, J, Tremolizzo, L, Department of Neurosciences, Neurologian yksikkö, Clinicum, HUS Neurocenter, Translational neuroradiology unit [Bethesda], National Institute of Neurological Disorders and Stroke [Bethesda] (NINDS), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Univ Granada, Hosp Univ Granada, Inst Invest Biosanitaria Ibs GRANADA, Escuela Andaluza Salud Publ, Granada, Spain, Partenaires INRAE, Queen Mary University of London (QMUL), University College of London [London] (UCL), University of Bristol [Bristol], Département de Physique, Université de Genève, Université de Genève (UNIGE), Università degli studi di Torino (UNITO), University G. d'Annunzio, Chieti, Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), Department of Neurology, A.O.U. Maggiore della Carità, and IRCAD, Novara, Department of Health Sciences, UPO University, UPO University, Dipartimento di Matematica 'Ulisse Dini', Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Department of Neurology, Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Department of Neuroscience, University of Siena, Siena, Università cattolica del Sacro Cuore [Roma] (Unicatt), Università degli studi di Bari Aldo Moro (UNIBA), Istituto di Genetica Medica, Centro Sclerosi Multipla, Ospedale Binaghi, Via Is Guadazzonis 2, Cagliari, Italy, University of Novara, IRCCS-Istituti Clinici Scientifici Maugeri, University of Milan, Milan, Italy, Department of Biomedical and Specialty Surgical Sciences, Università degli Studi di Ferrara (UniFE), S. Anna Hospital, Department of Neuroscience, Catholic University, Roma, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Institute of Medical Genetics, Catholic University, Rome, Italy, Department of Clinical Genetics, Department of Pathology University of Pittsburgh School of Medicine, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Princeton University, University of Illinois at Urbana-Champaign [Urbana], University of Illinois System, Centre référent Sclérose Latérale Amyotrophique [CHRU Montpellier] (SLA CHRU Montpellier), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Università degli Studi di Milano [Milano] (UNIMI), Laboratory of Neurogenetics, National Institute of Aging, Tel Aviv Sourasky Medical Center [Te Aviv], University of New Haven [Connecticut], Emory University [Atlanta, GA], UCL Institute of neurology, UCL Institute of Neurology, Cardiovascular, Renal and Metabolism, IMED Biotech Unit, AstraZeneca, Genomic Research Laboratory, Service of Infectious Disease, Hôpitaux Universitaires de Genève (HUG), Boston University [Boston] (BU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Biochimie [CHRU Nîmes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, University of California [Davis] (UC Davis), University of California-University of California, Tanz Center Research in Neurodegenerative Diseases [Toronto], University of Toronto, Johns Hopkins University, School of Medicine, Department of Medicine, Surgery, and Dentistry, University of Milano, Institute for Clinical Neurobiology, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Penn State Hershey Medical Center, Penn State Health Milton S. Hershey Medical Center, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Penn State System-Pennsylvania Commonwealth System of Higher Education (PCSHE)-Penn State System, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Perelman School of Medicine, University of Pennsylvania [Philadelphia], Metacohorts Consortium, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Helsinki, Merck Research Laboratories, National Institutes of Health [Bethesda] (NIH), Center for Neuroscience and Regenerative Medicine [Bethesda] (CNRM), Henry M. Jackson Foundation for the Advancement of Military Medicine (HJM)
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Linkage disequilibrium
Multifactorial Inheritance
Multivariate analysis
LD SCORE REGRESSION
DYSLIPIDEMIA
Genome-wide association study
3124 Neurology and psychiatry
0302 clinical medicine
PROTECTIVE FACTOR
Mendelian Randomization Analysis
3. Good health
ALZHEIMERS-DISEASE
Settore MED/26 - NEUROLOGIA
risk factor
BIAS
Neurology
CARDIOVASCULAR-DISEASE
MENDELIAN RANDOMIZATION
Amyotrophic lateral Sclerosis
LD score regression
Mendelian randomization
amyotrophic lateral sclerosis
public resource
Life Sciences & Biomedicine
Clinical psychology
Human
Clinical Neurology
Biology
NO
03 medical and health sciences
Humans
Genetic Predisposition to Disease
Mendelian Randomization Analysi
MESH: Amyotrophic Lateral Sclerosis
Genetic Predisposition to Disease / genetics
Genome-Wide Association Study / methods
Mendolian Randomization Analysis / methods
Exercise
Genetic association
Science & Technology
[SCCO.NEUR]Cognitive science/Neuroscience
Amyotrophic Lateral Sclerosis
3112 Neurosciences
Neurosciences
030104 developmental biology
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics
CHOLESTEROL HOMEOSTASIS
Causal inference
[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Neurosciences & Neurology
Neurology (clinical)
Genome-Wide Association Study
ALS
030217 neurology & neurosurgery
Amyotrophic Lateral Sclerosi
Zdroj: Annals of neurology 85 (2019): 470–481. doi:10.1002/ana.25431
info:cnr-pdr/source/autori:Bandres-Ciga S; Noyce AJ; Hemani G; Nicolas A; Calvo A; Mora G; Arosio A; Barberis M; Bartolomei I; Battistini S; Benigni M; Borghero G; Brunetti M; Cammarosano S; Cannas A; Canosa A; Capasso M; Caponnetto C; Caredda C; Carrera P; Casale F; Cavallaro S; Chiò A; Colletti T; Conforti FL; Conte A; Corrado L; Costantino E; D'Alfonso S; Fasano A; Femiano C; Ferrarese C; Fini N; Floris G; Fuda G; Giannini F; Grassano M; Ilardi A; La Bella V; Lattante S; Logroscino G; Logullo FO; Loi D; Lunetta C; Mancardi G; Mandich P; Mandrioli J; Manera U; Marangi G; Marinou K; Marrali G; Marrosu MG; Mazzini L; Melis M; Messina S; Moglia C; Monsurro MR; Mosca L; Occhineri P; Origone P; Pani C; Penco S; Petrucci A; Piccirillo G; Pirisi A; Pisano F; Pugliatti M; Restagno G; Ricci C; Rita Murru M; Riva N; Sabatelli M; Salvi F; Santarelli M; Sideri R; Simone I; Spataro R; Tanel R; Tedeschi G; Tranquilli S; Tremolizzo L; Trojsi F; Volanti P; Zollino M; Abramzon Y; Arepalli S; Baloh RH; Bowser R; Brady CB; Brice A; Broach J; Campbell RH; Camu W; Chia R; Cooper-Knock J; Cusi D; Ding J; Drepper C; Drory VE; Dunckley TL; Eicher JD; Faghri F; Feldman E; Kay Floeter M; Fratta P; Geiger JT; Gerhard G; Gibbs JR; Gibson SB; Glass JD; Hardy J; Harms MB; Heiman-Patterson TD; Hernandez DG; Jansson L; Kamel F; Kirby J; Kowall NW; Laaksovirta H; Landi F; Le Ber I; Lumbroso S; MacGowan DJL; Maragakis NJ; Mouzat K; Murphy NA; Myllykangas L; Nalls MA; Orrell RW; Ostrow LW; Pamphlett R; Pickering-Brown S; Pioro E; Pliner HA; Pulst SM; Ravits JM; Renton AE; Rivera A; Robbrecht W; Rogaeva E; Rollinson S; Rothstein JD; Salvi E; Scholz SW; Sendtner M; Shaw PJ; Sidle KC; Simmons Z; Singleton AB; Stone DC; Sulkava R; Tienari PJ; Traynor BJ; Trojanowski JQ; Troncoso JC; Van Damme P; Van Deerlin VM; Van Den Bosch L; Zinman L; Stone DJ;/titolo:Shared polygenic risk and causal inferences in amyotrophic lateral sclerosis/doi:10.1002%2Fana.25431/rivista:Annals of neurology/anno:2019/pagina_da:470/pagina_a:481/intervallo_pagine:470–481/volume:85
2019, ' Shared polygenic risk and causal inferences in amyotrophic lateral sclerosis ', Annals of Neurology, vol. 85, no. 4, pp. 470-481 . https://doi.org/10.1002/ana.25431
Annals of Neurology
Annals of Neurology, Wiley, 2019, 85 (4), pp.470-481. ⟨10.1002/ana.25431⟩
ISSN: 0364-5134
1531-8249
DOI: 10.1002/ana.25431
Popis: OBJECTIVE: To identify shared polygenic risk and causal associations in amyotrophic lateral sclerosis (ALS). METHODS: Linkage disequilibrium score regression and Mendelian randomization were applied in a large-scale, data-driven manner to explore genetic correlations and causal relationships between >700 phenotypic traits and ALS. Exposures consisted of publicly available genome-wide association studies (GWASes) summary statistics from MR Base and LD-hub. The outcome data came from the recently published ALS GWAS involving 20,806 cases and 59,804 controls. Multivariate analyses, genetic risk profiling, and Bayesian colocalization analyses were also performed. RESULTS: We have shown, by linkage disequilibrium score regression, that ALS shares polygenic risk genetic factors with a number of traits and conditions, including positive correlations with smoking status and moderate levels of physical activity, and negative correlations with higher cognitive performance, higher educational attainment, and light levels of physical activity. Using Mendelian randomization, we found evidence that hyperlipidemia is a causal risk factor for ALS and localized putative functional signals within loci of interest. INTERPRETATION: Here, we have developed a public resource (https://lng-nia.shinyapps.io/mrshiny) which we hope will become a valuable tool for the ALS community, and that will be expanded and updated as new data become available. Shared polygenic risk exists between ALS and educational attainment, physical activity, smoking, and tenseness/restlessness. We also found evidence that elevated low-desnity lipoprotein cholesterol is a causal risk factor for ALS. Future randomized controlled trials should be considered as a proof of causality. Ann Neurol 2019;85:470-481. ispartof: ANNALS OF NEUROLOGY vol:85 issue:4 pages:470-481 ispartof: location:United States status: published
Databáze: OpenAIRE
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