Back to Search
Start Over
Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis
- Source :
- Van Rheenen, W, Shatunov, A, Dekker, A M, Mclaughlin, R L, Diekstra, F P, Pulit, S L, Van Der Spek, R A A, Võsa, U, De Jong, S, Robinson, M R, Yang, J, Fogh, I, Van Doormaal, P T, Tazelaar, G H P, Koppers, M, Blokhuis, A M, Sproviero, W, Jones, A R, Kenna, K P, Van Eijk, K R, Harschnitz, O, Schellevis, R D, Brands, W J, Medic, J, Menelaou, A, Vajda, A, Ticozzi, N, Lin, K, Rogelj, B, Vrabec, K, Ravnik-glavač, M, Koritnik, B, Zidar, J, Leonardis, L, Grošelj, L D, Millecamps, S, Salachas, F, Meininger, V, De Carvalho, M, Pinto, S, Mora, J S, Rojas-garcía, R, Polak, M, Chandran, S, Colville, S, Swingler, R, Morrison, K E, Shaw, P J, Hardy, J, Orrell, R W, Pittman, A, Sidle, K, Fratta, P, Malaspina, A, Topp, S, Petri, S, Abdulla, S, Drepper, C, Sendtner, M, Meyer, T, Ophoff, R A, Staats, K A, Wiedau-pazos, M, Lomen-hoerth, C, Van Deerlin, V M, Trojanowski, J Q, Elman, L, Mccluskey, L, Basak, A N, Tunca, C, Hamzeiy, H, Parman, Y, Meitinger, T, Lichtner, P, Radivojkov-blagojevic, M, Andres, C R, Maurel, C, Bensimon, G, Landwehrmeyer, B, Brice, A, Payan, C A M, Saker-delye, S, Dürr, A, Wood, N W, Tittmann, L, Lieb, W, Franke, A, Rietschel, M, Cichon, S, Nöthen, M M, Amouyel, P, Tzourio, C, Dartigues, J, Uitterlinden, A G, Rivadeneira, F, Estrada, K, Hofman, A, Curtis, C, Blauw, H M, Van Der Kooi, A J, De Visser, M, Goris, A, Weber, M, Shaw, C E, Smith, B N, Pansarasa, O, Cereda, C, Del Bo, R, Comi, G P, D'alfonso, S, Bertolin, C, Sorarù, G, Mazzini, L, Pensato, V, Gellera, C, Tiloca, C, Ratti, A, Calvo, A, Moglia, C, Brunetti, M, Arcuti, S, Capozzo, R, Zecca, C, Lunetta, C, Penco, S, Riva, N, Padovani, A, Filosto, M, Muller, B, Stuit, R J, Blair, I, Zhang, K, Mccann, E P, Fifita, J A, Nicholson, G A, Rowe, D B, Pamphlett, R, Kiernan, M C, Grosskreutz, J, Witte, O W, Ringer, T, Prell, T, Stubendorff, B, Kurth, I, Hübner, C A, Leigh, P N, Casale, F, Chio, A, Beghi, E, Pupillo, E, Tortelli, R, Logroscino, G, Powell, J, Ludolph, A C, Weishaupt, J H, Robberecht, W, Van Damme, P, Franke, L, Pers, T H, Brown, R H, Glass, J D, Landers, J E, Hardiman, O, Andersen, P M, Corcia, P, Vourc'h, P, Silani, V, Wray, N R, Visscher, P M, De Bakker, P I W, Van Es, M A, Pasterkamp, R J, Lewis, C M, Breen, G, Al-chalabi, A, Van Den Berg, L H & Veldink, J H 2016, ' Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis ', Nature Genetics . https://doi.org/10.1038/ng.3622, Nature Genetics, 48(9), 1043-1050. Nature Publishing Group, NATURE GENETICS, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, instname, van Rheenen, W, Shatunov, A, Dekker, A M, McLaughlin, R L, Diekstra, F P, Pulit, S L, van der Spek, R A A, Võsa, U, de Jong, S, Robinson, M R, Yang, J, Fogh, I, van Doormaal, P T, Tazelaar, G H P, Koppers, M, Blokhuis, A M, Sproviero, W, Jones, A R, Kenna, K P, van Eijk, K R, Harschnitz, O, Schellevis, R D, Brands, W J, Medic, J, Menelaou, A, Vajda, A, Ticozzi, N, Lin, K, Rogelj, B, Vrabec, K, Ravnik-Glavač, M, Koritnik, B, Zidar, J, Leonardis, L, Grošelj, L D, Millecamps, S, Salachas, F, Meininger, V, de Carvalho, M, Pinto, S, Fratta, P, Topp, S, Curtis, C, Shaw, C E, Smith, B N, Leigh, P N, Powell, J, Lewis, C M, Breen, G, Al-Chalabi, A 2016, ' Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis ', Nature Genetics, vol. 48, pp. 1043–1048 . https://doi.org/10.1038/ng.3622, Nature Genetics, Nature Genetics, 48(9), 1043-1048. Nature Publishing Group, Nature genetics, 48(9), 1043-1048. Nature Publishing Group, Repositório Científico de Acesso Aberto de Portugal, Repositório Científico de Acesso Aberto de Portugal (RCAAP), instacron:RCAAP
- Publication Year :
- 2016
-
Abstract
- Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.<br />To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1-10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk.
- Subjects :
- 0301 basic medicine
Population
EFFICIENT
Genome-wide association study
Locus (genetics)
Biology
SUSCEPTIBILITY
SEQUENCE
Article
Cohort Studies
03 medical and health sciences
0302 clinical medicine
Munc18 Proteins
medicine
Journal Article
Genetics
Humans
Genetic Predisposition to Disease
Comparative Study
Amyotrophic lateral sclerosis
education
POPULATION
Genetic association
Netherlands
PITFALLS
education.field_of_study
HEXANUCLEOTIDE REPEAT
COMPLEX
Project MinE
Amyotrophic Lateral Sclerosis
Proteins
PATHWAYS
FRONTOTEMPORAL DEMENTIA
medicine.disease
Genetic architecture
Cytoskeletal Proteins
030104 developmental biology
Case-Control Studies
Mutation
ALS
030217 neurology & neurosurgery
Imputation (genetics)
Myelin Proteins
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 10614036
- Database :
- OpenAIRE
- Journal :
- Van Rheenen, W, Shatunov, A, Dekker, A M, Mclaughlin, R L, Diekstra, F P, Pulit, S L, Van Der Spek, R A A, Võsa, U, De Jong, S, Robinson, M R, Yang, J, Fogh, I, Van Doormaal, P T, Tazelaar, G H P, Koppers, M, Blokhuis, A M, Sproviero, W, Jones, A R, Kenna, K P, Van Eijk, K R, Harschnitz, O, Schellevis, R D, Brands, W J, Medic, J, Menelaou, A, Vajda, A, Ticozzi, N, Lin, K, Rogelj, B, Vrabec, K, Ravnik-glavač, M, Koritnik, B, Zidar, J, Leonardis, L, Grošelj, L D, Millecamps, S, Salachas, F, Meininger, V, De Carvalho, M, Pinto, S, Mora, J S, Rojas-garcía, R, Polak, M, Chandran, S, Colville, S, Swingler, R, Morrison, K E, Shaw, P J, Hardy, J, Orrell, R W, Pittman, A, Sidle, K, Fratta, P, Malaspina, A, Topp, S, Petri, S, Abdulla, S, Drepper, C, Sendtner, M, Meyer, T, Ophoff, R A, Staats, K A, Wiedau-pazos, M, Lomen-hoerth, C, Van Deerlin, V M, Trojanowski, J Q, Elman, L, Mccluskey, L, Basak, A N, Tunca, C, Hamzeiy, H, Parman, Y, Meitinger, T, Lichtner, P, Radivojkov-blagojevic, M, Andres, C R, Maurel, C, Bensimon, G, Landwehrmeyer, B, Brice, A, Payan, C A M, Saker-delye, S, Dürr, A, Wood, N W, Tittmann, L, Lieb, W, Franke, A, Rietschel, M, Cichon, S, Nöthen, M M, Amouyel, P, Tzourio, C, Dartigues, J, Uitterlinden, A G, Rivadeneira, F, Estrada, K, Hofman, A, Curtis, C, Blauw, H M, Van Der Kooi, A J, De Visser, M, Goris, A, Weber, M, Shaw, C E, Smith, B N, Pansarasa, O, Cereda, C, Del Bo, R, Comi, G P, D'alfonso, S, Bertolin, C, Sorarù, G, Mazzini, L, Pensato, V, Gellera, C, Tiloca, C, Ratti, A, Calvo, A, Moglia, C, Brunetti, M, Arcuti, S, Capozzo, R, Zecca, C, Lunetta, C, Penco, S, Riva, N, Padovani, A, Filosto, M, Muller, B, Stuit, R J, Blair, I, Zhang, K, Mccann, E P, Fifita, J A, Nicholson, G A, Rowe, D B, Pamphlett, R, Kiernan, M C, Grosskreutz, J, Witte, O W, Ringer, T, Prell, T, Stubendorff, B, Kurth, I, Hübner, C A, Leigh, P N, Casale, F, Chio, A, Beghi, E, Pupillo, E, Tortelli, R, Logroscino, G, Powell, J, Ludolph, A C, Weishaupt, J H, Robberecht, W, Van Damme, P, Franke, L, Pers, T H, Brown, R H, Glass, J D, Landers, J E, Hardiman, O, Andersen, P M, Corcia, P, Vourc'h, P, Silani, V, Wray, N R, Visscher, P M, De Bakker, P I W, Van Es, M A, Pasterkamp, R J, Lewis, C M, Breen, G, Al-chalabi, A, Van Den Berg, L H & Veldink, J H 2016, ' Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis ', Nature Genetics . https://doi.org/10.1038/ng.3622, Nature Genetics, 48(9), 1043-1050. Nature Publishing Group, NATURE GENETICS, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, instname, van Rheenen, W, Shatunov, A, Dekker, A M, McLaughlin, R L, Diekstra, F P, Pulit, S L, van der Spek, R A A, Võsa, U, de Jong, S, Robinson, M R, Yang, J, Fogh, I, van Doormaal, P T, Tazelaar, G H P, Koppers, M, Blokhuis, A M, Sproviero, W, Jones, A R, Kenna, K P, van Eijk, K R, Harschnitz, O, Schellevis, R D, Brands, W J, Medic, J, Menelaou, A, Vajda, A, Ticozzi, N, Lin, K, Rogelj, B, Vrabec, K, Ravnik-Glavač, M, Koritnik, B, Zidar, J, Leonardis, L, Grošelj, L D, Millecamps, S, Salachas, F, Meininger, V, de Carvalho, M, Pinto, S, Fratta, P, Topp, S, Curtis, C, Shaw, C E, Smith, B N, Leigh, P N, Powell, J, Lewis, C M, Breen, G, Al-Chalabi, A 2016, ' Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis ', Nature Genetics, vol. 48, pp. 1043–1048 . https://doi.org/10.1038/ng.3622, Nature Genetics, Nature Genetics, 48(9), 1043-1048. Nature Publishing Group, Nature genetics, 48(9), 1043-1048. Nature Publishing Group, Repositório Científico de Acesso Aberto de Portugal, Repositório Científico de Acesso Aberto de Portugal (RCAAP), instacron:RCAAP
- Accession number :
- edsair.doi.dedup.....0b15b973eef3492fa234ec27a3981a5c