Citations 2
Common and rare variant association analyses in Amyotrophic Lateral Sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
Rheenen, Wouter van , Spek, Rick van der, Berg, Leonard van den, Hop, Paul , Zwamborn, Ramona, Klein, Niek de , Westra, Harm-Jan , Bakker, Olivier, Shireby, Gemma , Dolzhenko, Egor, Dekker, Annelot, Westeneng, Henk-Jan, Tazelaar, Gijs, Eijk, Kristel van , Kooyman, Maarten , Doherty, Mark, Iacoangeli, Alfredo, Cooper‐Knock, Johnathan , Smith, Bradley , Chandran, Siddharthan , Morrison, Karen, Shaw, Pamela, Hardy, John , Orrell, Richard, Basak, Nazli, Ratti, Antonia, Pinter, Guiseppe Lauria, D'Alfonso, Sandra, Soraru, Gianni, Padovani, Alessandro , Moglia, Cristina, Brunetti, Maura, Canosa, Antonio, Grassano, Maurizio, Nefussy, Beatrice, Nordin, Angelica, Lerner, Yossef, Zabari, Michal, Baloh, Robert, Bell, Shaugn, Vourc'h, Patrick, Corcia, Philippe, Couratier, Philippe, Meininger, Vincent, Salachas, Francois, Pardina, Jesús Mora, Assialioui, Abdelilah , Rojas‐García, Ricardo , Dion, Patrick, Ludolph, Albert, Weishaupt, Jochen, Brenner, David, Freischmidt, Axel , Bensimon, Gilbert , Durr, Alexandra, Payan, Christine, Saker-Delye, Safa, Wood, Nicholas , Rademakers, Rosa, Tittmann, Lukas, Lieb, Wolfgang, Braun, Alice, Hofman, Albert, Cichon, Sven , Traynor, Bryan, Singleton, Andrew, Neto, Miguel Mitne, Ophoff, Roel, Wiedau-Pazos, Martina, Lomen-Hoerth, Catherine, Rödiger, Annekathrin, Jörk, Alexander, Barthel, Tabea, Theele, Erik, Ilse, Berjamin, Stubendorff, Beatrice, Witte, Otto W. , Hübner, Christian, Graff, Caroline , Brylev, Lev, Fominykh, Vera, Demeshonok, Vera, Ataulina, Anastasia , Koritnik, Blaž , Zidar, Janez , Ravnik-Glavač, Metka, Glavač, Damjan, Stević, Zorica, Drory, Vivian, Povedano, Mónica, Henderson, Robert , Furlong, Sarah , McCombe, Pamela, Ngo, Shyuan, Steyn, Frederik, Mather, Karen A. , Sachdev, Perminder S. , Henders, Anjali, Carvalho, Mamede de, Petri, Susanne, Weber, Markus , Glass, Jonathan D. , Brown, Robert, Landers, John, Garton, Fleur, McRae, Allan, Mill, Jonathan , Kenna, Kevin, Runz, Heiko, Franke, Lude , Damme, Philip Van , Gaur, Nayana , Steyn, Frederik J. , Landers, John E. , Westra, Harm-Jan , Steyn, F J , Cichon, Sven , Sachdev, Perminder S , Van Damme, Philip , Hardy, John , Padovani, Alessandro , Graff, Caroline , Spek, Rick A. A. van der , Bakker, Mark K. , Veldink, Jan H. , Vugt, Joke J.F.A. van , Zwamborn, Ramona A.J. , Deelen, Patrick , Hannon, Eilís , Moisse, Matthieu , Baird, Denis A. , Restuadi, Restuadi , Gawor, Klara , Westeneng, Henk‐Jan , Byrne, Ross Patrick , Heverin, Mark , Khleifat, Ahmad Al , Iacoangeli, Alfredo , Shatunov, Aleksey , Ticozzi, Nicola , Gromicho, Marta , Pal, Suvankar , Orrell, Richard W., Sendtner, Michael , Meyer, Thomas , Basak, Nazli A., Kooi, Anneke J. van der , Ratti, Antonia , Fogh, Isabella , Gellera, Cinzia , Corti, Stefania Paola , Cereda, Cristina , Sproviero, Daisy , D’Alfonso, Sandra , Siciliano, Gabriele , Filosto, Massimiliano , Chiò, Adriano , Calvo, Andrea , Moglia, Cristina , Brunetti, Maura , Canosa, Antonio , Grassano, Maurizio , Beghi, Ettore , Pupillo, Elisabetta , Logroscino, Giancarlo , Osmanovic, Alma , Nordin, Angelica , Lerner, Yossef, Zabari, Michal, Gotkine, Marc , Vourc’h, Patrick , Corcia, Philippe , Couratier, Philippe , Millecamps, Stéphanie , Meininger, Vincent, Salachas, François, Ross, Jay P. , Ludolph, Albert, Brice, Alexis , Dürr, Alexandra , Saker-Delye, Safaa, Wood, Nicholas , Topp, Simon , Rademakers, Rosa , Tittmann, Lukas , Franke, André , Ripke, Stephan , Braun, Alice , Kraft, Julia , Whiteman, David C. , Olsen, Catherine M. , Uitterlinden, André G. , Hofman, Albert, Rietschel, Marcella , Nöthen, Markus M. , Amouyel, Philippe , Traynor, Bryan J. , Singleton, Andrew, Cauchi, Ruben J. , Ophoff, Roel A. , Lomen‐Hoerth, Catherine , Deerlin, Vivianna M. Van , Großkreutz, Julian , Rödiger, Annekathrin, Jörk, Alexander, Barthel, Tabea, Theele, Erik, Steinbach, Robert , Hübner, Christian, Fominykh, Vera , Demeshonok, Vera, Rogelj, Boris , Drory, Vivian, Blair, Ian P. , Kiernan, Matthew C. , Benyamin, Beben , Mathers, Susan , Needham, Merrilee , Ngo, Shyuan T. , Nicholson, Garth A. , Pamphlett, Roger , Rowe, Dominic B. , Williams, Kelly L. , Wallace, Leanne M. , Carvalho, Mamede A. de , Pinto, Susana , Petri, Susanne , Rouleau, Guy Armand , Silani, Vincenzo , Curtis, Charles J. C. , Breen, Gerome , Brown, Robert, Shaw, Christopher E. , Andersen, Peter Munch , Groen, Ewout J. N. , Es, Michael A. van , Pasterkamp, R. Jeroen , Fan, Dongsheng , Smith, George Davey , Gaunt, Tom R. , Eberle, Michael A. , McLaughlin, Russell L. , Hardiman, Orla , Wray, Naomi , Tsai, Ellen A. , Runz, Heiko , Al‐Chalabi, Ammar
No container title available | March 18, 2021 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a life-time risk of 1 in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry GWAS in ALS including 29,612 ALS patients and 122,656 controls which identified 15 risk loci in ALS. When combined with 8,953 whole-genome sequenced individuals (6,538 ALS patients, 2,415 controls) and the largest cortex-derived eQTL dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, repeat expansions or regulatory effects. ALS associated risk loci were shared with multiple traits within the neurodegenerative spectrum, but with distinct enrichment patterns across brain regions and cell-types. Of the environmental and life-style risk factors obtained from literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. All ALS associated signals combined reveal a role for perturbations in vesicle mediated transport and autophagy, and provide evidence for cell-autonomous disease initiation in glutamatergic neurons.
Full sequencing and haplotype analysis of MAPT in Parkinson's disease and rapid eye movement sleep behavior disorder
Li, Jiao , Ruskey, Jennifer A. , Arnulf, Isabelle , Dauvilliers, Yves , Hu, Michele T.M., Högl, Birgit , Leblond, Claire S. , Ambalavanan, Amirthagowri , Ross, Jay P. , Bourassa, Cynthia V., Spiegelman, Dan , Laurent, Sandra B., Stefani, Ambra , Monaca, Christelle, Boivin, Michel , Antelmi, Elena , Young, Peter, Heidbreder, Anna , Ferman, Tanis J. , Dion, Patrick A. , Désautels, Alex , Gagnon, Jean‐François, Dupré, Nicolas , Montplaisir, Jacques , Boeve, Bradley F., Ross, Owen A. , Shulman, Joshua , Labbé, Catherine, Antelmi, Elena , Ross, Owen A , Dauvilliers, Yves , Ferman, Tanis J , Stefani, Ambra , Zhou, Sirui , Cochen De Cock, Valérie , Ferini-Strambi, Luigi , Plazzi, Giuseppe , Labbé, Catherine , Fan, Dongsheng , Fon, Edward A , Boeve, Bradley F. , Postuma, Ronald B. , Rouleau, Guy Armand , Gan‐Or, Ziv , Arnulf, Isabelle , Hu, Michele T M , Högl, Birgit , Heidbreder, Anna
Movement Disorders | May 14, 2018 | Volume: 33 | Issue: 6 | Pages: 1016-1020
ABSTRACT Background: MAPT haplotypes are associated with PD, but their association with rapid eye movement sleep behavior disorder is unclear. Objective: To study the role of MAPT variants in rapid eye movement sleep behavior disorder. Methods: Two cohorts were included: (A) PD (n = 600), rapid eye movement sleep behavior disorder (n = 613) patients, and controls (n = 981); (B) dementia with Lewy bodies patients with rapid eye movement sleep behavior disorder (n = 271) and controls (n = 950). MAPT ‐associated variants and the entire coding sequence of MAPT were analyzed. Age‐, sex‐, and ethnicity‐adjusted analyses were performed to examine the association between MAPT , PD, and rapid eye movement sleep behavior disorder. Results: MAPT‐ H2 variants were associated with PD (odds ratios: 0.62‐0.65; P = 0.010‐0.019), but not with rapid eye movement sleep behavior disorder. In PD, the H1 haplotype odds ratio was 1.60 (95% confidence interval: 1.12‐2.28; P = 0.009), and the H2 odds ratio was 0.68 (95% confidence interval: 0.48‐0.96; P = 0.03). The H2/H1 haplotypes were not associated with rapid eye movement sleep behavior disorder. Conclusions: Our results confirm the protective effect of the MAPT ‐H2 haplotype in PD, and define its components. Furthermore, our results suggest that MAPT does not play a major role in rapid eye movement sleep behavior disorder, emphasizing different genetic background than in PD in this locus. © 2018 International Parkinson and Movement Disorder Society