171 results on '"Vilariño-Güell, Carles"'
Search Results
2. Exome sequencing study in patients with multiple sclerosis reveals variants associated with disease course
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Gil-Varea, Elia, Urcelay, Elena, Vilariño-Güell, Carles, Costa, Carme, Midaglia, Luciana, Matesanz, Fuencisla, Rodríguez-Antigüedad, Alfredo, Oksenberg, Jorge, Espino-Paisan, Laura, Dessa Sadovnick, A, Saiz, Albert, Villar, Luisa M, García-Merino, Juan Antonio, Ramió-Torrentà, Lluís, Triviño, Juan Carlos, Quintana, Ester, Robles, René, Sánchez-López, Antonio, Arroyo, Rafael, Alvarez-Cermeño, Jose C, Vidal-Jordana, Angela, Malhotra, Sunny, Fissolo, Nicolas, Montalban, Xavier, and Comabella, Manuel
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Biomedical and Clinical Sciences ,Neurosciences ,Immunology ,Autoimmune Disease ,Human Genome ,Multiple Sclerosis ,Neurodegenerative ,Genetics ,Brain Disorders ,Clinical Research ,4.2 Evaluation of markers and technologies ,Detection ,screening and diagnosis ,Aetiology ,2.1 Biological and endogenous factors ,Neurological ,Brain ,Carboxypeptidases A ,Cohort Studies ,Disease Progression ,Female ,Gene Frequency ,Genetic Predisposition to Disease ,Genotype ,Humans ,Immunoglobulins ,Male ,Nerve Tissue Proteins ,Polymorphism ,Single Nucleotide ,RNA ,Messenger ,Exome Sequencing ,Multiple sclerosis ,Disease course ,Exome sequencing ,Polymorphisms ,CPXM2 ,IGSF9B ,NLRP9 ,Clinical Sciences ,Neurology & Neurosurgery - Abstract
BackgroundIt remains unclear whether disease course in multiple sclerosis (MS) is influenced by genetic polymorphisms. Here, we aimed to identify genetic variants associated with benign and aggressive disease courses in MS patients.MethodsMS patients were classified into benign and aggressive phenotypes according to clinical criteria. We performed exome sequencing in a discovery cohort, which included 20 MS patients, 10 with benign and 10 with aggressive disease course, and genotyping in 2 independent validation cohorts. The first validation cohort encompassed 194 MS patients, 107 with benign and 87 with aggressive phenotypes. The second validation cohort comprised 257 patients, of whom 224 patients had benign phenotypes and 33 aggressive disease courses. Brain immunohistochemistries were performed using disease course associated genes antibodies.ResultsBy means of single-nucleotide polymorphism (SNP) detection and comparison of allele frequencies between patients with benign and aggressive phenotypes, a total of 16 SNPs were selected for validation from the exome sequencing data in the discovery cohort. Meta-analysis of genotyping results in two validation cohorts revealed two polymorphisms, rs28469012 and rs10894768, significantly associated with disease course. SNP rs28469012 is located in CPXM2 (carboxypeptidase X, M14 family, member 2) and was associated with aggressive disease course (uncorrected p value
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- 2018
3. Exome-wide rare variant analysis in familial essential tremor
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Diez-Fairen, Monica, Houle, Gabrielle, Ortega-Cubero, Sara, Bandres-Ciga, Sara, Alvarez, Ignacio, Carcel, Maria, Ibañez, Laura, Fernandez, Maria Victoria, Budde, John P., Trotta, Jean-Rémi, Tonda, Raúl, Chong, Jessica X., Bamshad, Michael J., Nickerson, Deborah A., Aguilar, Miquel, Tartari, Juan P., Gironell, Alexandre, García-Martín, Elena, Agundez, Jose AG., Alonso-Navarro, Hortensia, Jimenez-Jimenez, Felix Javier, Fernandez, Manel, Valldeoriola, Francesc, Marti, Maria Jose, Tolosa, Eduard, Coria, Francisco, Pastor, Maria A., Vilariño-Güell, Carles, Rajput, Alex, Dion, Patrick A., Cruchaga, Carlos, Rouleau, Guy A., and Pastor, Pau
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- 2021
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4. Genetic analysis of nucleotide-binding leucine-rich repeat (NLR) receptors in multiple sclerosis
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Popplewell, Lisa F., Encarnacion, Mary, Bernales, Cecily Q., Sadovnick, A Dessa, Traboulsee, Anthony L., Quandt, Jacqueline A., and Vilariño-Güell, Carles
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- 2020
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5. Absence of Mutation Enrichment for Genes Phylogenetically Conserved in the Olivocerebellar Motor Circuitry in a Cohort of Canadian Essential Tremor Cases
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Schmouth, Jean-François, Houle, Gabrielle, Ambalavanan, Amirthagowri, Leblond, Claire S., Spiegelman, Dan, Laurent, Sandra B., Bourassa, Cynthia V., Panisset, Michel, Chouinard, Sylvain, Dupré, Nicolas, Vilariño-Güell, Carles, Rajput, Alex, Dion, Patrick A., and Rouleau, Guy A.
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- 2019
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6. Genetic modifiers of multiple sclerosis progression, severity and onset
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Sadovnick, A. Dessa, Traboulsee, Anthony L., Zhao, Yinshan, Bernales, Cecily Q., Encarnacion, Mary, Ross, Jay P., Yee, Irene M., Criscuoli, Maria G., and Vilariño-Güell, Carles
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- 2017
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7. Oligodendrocyte ARNT2 expression is altered in models of MS
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Becquart, Pierre, Johnston, Jake, Vilariño-Güell, Carles, and Quandt, Jacqueline A.
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- 2020
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8. TPP2 mutation associated with sterile brain inflammation mimicking MS
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Reinthaler, Eva M., Graf, Elisabeth, Zrzavy, Tobias, Wieland, Thomas, Hotzy, Christoph, Kopecky, Chantal, Pferschy, Sandra, Schmied, Christiane, Leutmezer, Fritz, Keilani, Mohammad, Lill, Christina M., Hoffjan, Sabine, Epplen, Jörg T., Zettl, Uwe K., Hecker, Michael, Deutschländer, Angela, Meuth, Sven G., Ahram, Mamoun, Mustafa, Baha, El-Khateeb, Mohammed, Vilariño-Güell, Carles, Sadovnick, A. Dessa, Zimprich, Fritz, Tomkinson, Birgitta, Strom, Tim, Kristoferitsch, Wolfgang, Lassmann, Hans, and Zimprich, Alexander
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- 2018
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9. Mitochondrial DNA heteroplasmy distinguishes disease manifestation in PINK1/PRKN-linked Parkinson’s disease
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Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB) [research center], Fonds National de la Recherche - FnR (ProtectMove, MiRisk) [sponsor], DFG (ProtectMove) [sponsor], BMBF (MitoPD) [sponsor], Trinh, Joanne, Hicks, Andrew A., König, Inke R., Delcambre, Sylvie, Lüth, Theresa, Schaake, Susen, Wasner, Kobi, Ghelfi, Jenny, Borsche, Max, Vilariño-Güell, Carles, Hentati, Faycel, Germer, Elisabeth L., Bauer, Peter, Takanashi, Masashi, Kostić, Vladimir, Lang, Anthony E., Brüggemann, Norbert, Pramstaller, Peter P., Pichler, Irene, Rajput, Alex, Hattori, Nobutaka, Farrer, Matthew J., Lohmann, Katja, Weissensteiner, Hansi, May, Patrick, Klein, Christine, Grünewald, Anne, Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB) [research center], Fonds National de la Recherche - FnR (ProtectMove, MiRisk) [sponsor], DFG (ProtectMove) [sponsor], BMBF (MitoPD) [sponsor], Trinh, Joanne, Hicks, Andrew A., König, Inke R., Delcambre, Sylvie, Lüth, Theresa, Schaake, Susen, Wasner, Kobi, Ghelfi, Jenny, Borsche, Max, Vilariño-Güell, Carles, Hentati, Faycel, Germer, Elisabeth L., Bauer, Peter, Takanashi, Masashi, Kostić, Vladimir, Lang, Anthony E., Brüggemann, Norbert, Pramstaller, Peter P., Pichler, Irene, Rajput, Alex, Hattori, Nobutaka, Farrer, Matthew J., Lohmann, Katja, Weissensteiner, Hansi, May, Patrick, Klein, Christine, and Grünewald, Anne
- Abstract
Biallelic mutations in PINK1/PRKN cause recessive Parkinson’s disease. Given the established role of PINK1/Parkin in regulating mitochondrial dynamics, we explored mitochondrial DNA (mtDNA) integrity and inflammation as disease modifiers in carriers of mutations in these genes. MtDNA integrity was investigated in a large collection of biallelic (n = 84) and monoallelic (n = 170) carriers of PINK1/PRKN mutations, idiopathic Parkinson’s disease patients (n = 67) and controls (n = 90). In addition, we studied global gene expression and serum cytokine levels in a subset. Affected and unaffected PINK1/PRKN monoallelic mutation carriers can be distinguished by heteroplasmic mtDNA variant load (AUC = 0.83, CI:0.74-0.93). Biallelic PINK1/PRKN mutation carriers harbor more heteroplasmic mtDNA variants in blood (p = 0.0006, Z = 3.63) compared to monoallelic mutation carriers. This enrichment was confirmed in iPSC-derived (controls, n = 3; biallelic PRKN mutation carriers, n = 4) and postmortem (control, n = 1; biallelic PRKN mutation carrier, n = 1) midbrain neurons. Lastly, the heteroplasmic mtDNA variant load correlated with IL6 levels in PINK1/PRKN mutation carriers (r = 0.57, p = 0.0074). PINK1/PRKN mutations predispose individuals to mtDNA variant accumulation in a dose- and disease-dependent manner.
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- 2023
10. Analysis of galanin receptor GALR2 in multiple sclerosis
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Encarnacion, Mary, Bernales, Cecily Q., Traboulsee, Anthony L., Sadovnick, A. Dessa, and Vilariño-Güell, Carles
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- 2019
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11. A Whole-Genome Sequencing Study Implicates GRAMD1B in Multiple Sclerosis Susceptibility
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Esposito, Federica, primary, Osiceanu, Ana Maria, additional, Sorosina, Melissa, additional, Ottoboni, Linda, additional, Bollman, Bryan, additional, Santoro, Silvia, additional, Bettegazzi, Barbara, additional, Zauli, Andrea, additional, Clarelli, Ferdinando, additional, Mascia, Elisabetta, additional, Calabria, Andrea, additional, Zacchetti, Daniele, additional, Capra, Ruggero, additional, Ferrari, Maurizio, additional, Provero, Paolo, additional, Lazarevic, Dejan, additional, Cittaro, Davide, additional, Carrera, Paola, additional, Patsopoulos, Nikolaos, additional, Toniolo, Daniela, additional, Sadovnick, A Dessa, additional, Martino, Gianvito, additional, De Jager, Philip L., additional, Comi, Giancarlo, additional, Stupka, Elia, additional, Vilariño-Güell, Carles, additional, Piccio, Laura, additional, and Martinelli Boneschi, Filippo, additional
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- 2022
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12. Mitochondrial DNA heteroplasmy distinguishes disease manifestation in PINK1/PRKN-linked Parkinson’s disease
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Trinh, Joanne, primary, Hicks, Andrew A, additional, König, Inke R, additional, Delcambre, Sylvie, additional, Lüth, Theresa, additional, Schaake, Susen, additional, Wasner, Kobi, additional, Ghelfi, Jenny, additional, Borsche, Max, additional, Vilariño-Güell, Carles, additional, Hentati, Faycel, additional, Germer, Elisabeth L, additional, Bauer, Peter, additional, Takanashi, Masashi, additional, Kostić, Vladimir, additional, Lang, Anthony E, additional, Brüggemann, Norbert, additional, Pramstaller, Peter P, additional, Pichler, Irene, additional, Rajput, Alex, additional, Hattori, Nobutaka, additional, Farrer, Matthew J, additional, Lohmann, Katja, additional, Weissensteiner, Hansi, additional, May, Patrick, additional, Klein, Christine, additional, and Grünewald, Anne, additional
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- 2022
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13. Analysis of NOD-like receptor NLRP1 in multiple sclerosis families
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Bernales, Cecily Q., Encarnacion, Mary, Criscuoli, Maria G., Yee, Irene M., Traboulsee, Anthony L., Sadovnick, A. Dessa, and Vilariño-Güell, Carles
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- 2018
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14. Common genetic etiology between “multiple sclerosis-like” single-gene disorders and familial multiple sclerosis
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Traboulsee, Anthony L., Sadovnick, A. Dessa, Encarnacion, Mary, Bernales, Cecily Q., Yee, Irene M., Criscuoli, Maria G., and Vilariño-Güell, Carles
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- 2017
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15. No rare deleterious variants from STK32B, PPARGC1A, and CTNNA3 are associated with essential tremor
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Houle, Gabrielle, Ambalavanan, Amirthagowri, Schmouth, Jean-François, Leblond, Claire S., Spiegelman, Dan, Laurent, Sandra B., Bourassa, Cynthia V., Grayson, Celene, Panisset, Michel, Chouinard, Sylvain, Dupré, Nicolas, Vilariño-Güell, Carles, Rajput, Alex, Girard, Simon L., Dion, Patrick A., and Rouleau, Guy A.
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- 2017
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16. Mitochondrial DNA heteroplasmy distinguishes disease manifestation in PINK1/PRKN-linked Parkinson's disease.
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Trinh, Joanne, Hicks, Andrew A, König, Inke R, Delcambre, Sylvie, Lüth, Theresa, Schaake, Susen, Wasner, Kobi, Ghelfi, Jenny, Borsche, Max, Vilariño-Güell, Carles, Hentati, Faycel, Germer, Elisabeth L, Bauer, Peter, Takanashi, Masashi, Kostić, Vladimir, Lang, Anthony E, Brüggemann, Norbert, Pramstaller, Peter P, Pichler, Irene, and Rajput, Alex
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MITOCHONDRIAL DNA ,PARKINSON'S disease ,GENE expression ,MELAS syndrome ,LEBER'S hereditary optic atrophy - Abstract
Biallelic mutations in PINK1 / PRKN cause recessive Parkinson's disease. Given the established role of PINK1/Parkin in regulating mitochondrial dynamics, we explored mitochondrial DNA integrity and inflammation as disease modifiers in carriers of mutations in these genes. Mitochondrial DNA integrity was investigated in a large collection of biallelic (n = 84) and monoallelic (n = 170) carriers of PINK1 / PRKN mutations, idiopathic Parkinson's disease patients (n = 67) and controls (n = 90). In addition, we studied global gene expression and serum cytokine levels in a subset. Affected and unaffected PINK1 / PRKN monoallelic mutation carriers can be distinguished by heteroplasmic mitochondrial DNA variant load (area under the curve = 0.83, CI 0.74–0.93). Biallelic PINK1 / PRKN mutation carriers harbour more heteroplasmic mitochondrial DNA variants in blood (P = 0.0006, Z = 3.63) compared to monoallelic mutation carriers. This enrichment was confirmed in induced pluripotent stem cell-derived (controls, n = 3; biallelic PRKN mutation carriers, n = 4) and post-mortem (control, n = 1; biallelic PRKN mutation carrier, n = 1) midbrain neurons. Last, the heteroplasmic mitochondrial DNA variant load correlated with IL6 levels in PINK1 / PRKN mutation carriers (r = 0.57, P = 0.0074). PINK1 / PRKN mutations predispose individuals to mitochondrial DNA variant accumulation in a dose- and disease-dependent manner. [ABSTRACT FROM AUTHOR]
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- 2023
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17. Mitochondrial DNA heteroplasmy distinguishes disease manifestation in PINK1- and PRKN-linked Parkinson’s disease
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Trinh, Joanne, primary, Hicks, Andrew A., additional, König, Inke R., additional, Delcambre, Sylvie, additional, Lüth, Theresa, additional, Schaake, Susen, additional, Wasner, Kobi, additional, Ghelfi, Jenny, additional, Borsche, Max, additional, Vilariño-Güell, Carles, additional, Hentati, Faycel, additional, Germer, Elisabeth L., additional, Bauer, Peter, additional, Takanashi, Masashi, additional, Kostić, Vladimir, additional, Lang, Anthony E., additional, Brüggemann, Norbert, additional, Pramstaller, Peter P., additional, Pichler, Irene, additional, Rajput, Alex, additional, Hattori, Nobutaka, additional, Farrer, Matthew J., additional, Lohmann, Katja, additional, Weissensteiner, Hansi, additional, May, Patrick, additional, Klein, Christine, additional, and Grünewald, Anne, additional
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- 2022
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18. Mitochondrial DNA heteroplasmy distinguishes disease manifestation in PINK1/PRKN-linked Parkinson’s disease
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Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB) [research center], Fonds National de la Recherche - FnR (ProtectMove, MiRisk) [sponsor], DFG (ProtectMove) [sponsor], BMBF (MitoPD) [sponsor], Trinh, Joanne, Hicks, Andrew A., König, Inke R., Delcambre, Sylvie, Lüth, Theresa, Schaake, Susen, Wasner, Kobi, Ghelfi, Jenny, Borsche, Max, Vilariño-Güell, Carles, Hentati, Faycel, Germer, Elisabeth L., Bauer, Peter, Takanashi, Masashi, Kostić, Vladimir, Lang, Anthony E., Brüggemann, Norbert, Pramstaller, Peter P., Pichler, Irene, Rajput, Alex, Hattori, Nobutaka, Farrer, Matthew J., Lohmann, Katja, Weissensteiner, Hansi, May, Patrick, Klein, Christine, Grünewald, Anne, Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB) [research center], Fonds National de la Recherche - FnR (ProtectMove, MiRisk) [sponsor], DFG (ProtectMove) [sponsor], BMBF (MitoPD) [sponsor], Trinh, Joanne, Hicks, Andrew A., König, Inke R., Delcambre, Sylvie, Lüth, Theresa, Schaake, Susen, Wasner, Kobi, Ghelfi, Jenny, Borsche, Max, Vilariño-Güell, Carles, Hentati, Faycel, Germer, Elisabeth L., Bauer, Peter, Takanashi, Masashi, Kostić, Vladimir, Lang, Anthony E., Brüggemann, Norbert, Pramstaller, Peter P., Pichler, Irene, Rajput, Alex, Hattori, Nobutaka, Farrer, Matthew J., Lohmann, Katja, Weissensteiner, Hansi, May, Patrick, Klein, Christine, and Grünewald, Anne
- Abstract
Biallelic mutations in PINK1/PRKN cause recessive Parkinson’s disease. Given the established role of PINK1/Parkin in regulating mitochondrial dynamics, we explored mitochondrial DNA (mtDNA) integrity and inflammation as disease modifiers in carriers of mutations in these genes. MtDNA integrity was investigated in a large collection of biallelic (n = 84) and monoallelic (n = 170) carriers of PINK1/PRKN mutations, idiopathic Parkinson’s disease patients (n = 67) and controls (n = 90). In addition, we studied global gene expression and serum cytokine levels in a subset. Affected and unaffected PINK1/PRKN monoallelic mutation carriers can be distinguished by heteroplasmic mtDNA variant load (AUC = 0.83, CI:0.74-0.93). Biallelic PINK1/PRKN mutation carriers harbor more heteroplasmic mtDNA variants in blood (p = 0.0006, Z = 3.63) compared to monoallelic mutation carriers. This enrichment was confirmed in iPSC-derived (controls, n = 3; biallelic PRKN mutation carriers, n = 4) and postmortem (control, n = 1; biallelic PRKN mutation carrier, n = 1) midbrain neurons. Lastly, the heteroplasmic mtDNA variant load correlated with IL6 levels in PINK1/PRKN mutation carriers (r = 0.57, p = 0.0074). PINK1/PRKN mutations predispose individuals to mtDNA variant accumulation in a dose- and disease-dependent manner.
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- 2022
19. Teneurin transmembrane protein 4 is not a cause for essential tremor in a Canadian population
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Houle, Gabrielle, Schmouth, Jean‐François, Leblond, Claire S., Ambalavanan, Amirthagowri, Spiegelman, Dan, Laurent, Sandra B., Bourassa, Cynthia V., Panisset, Michel, Chouinard, Sylvain, Dupré, Nicolas, Vilariño‐Güell, Carles, Rajput, Alex, Dion, Patrick A., and Rouleau, Guy A.
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- 2017
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20. Heterozygous PINK1 p.G411S increases risk of Parkinson’s disease via a dominant-negative mechanism
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Puschmann, Andreas, Fiesel, Fabienne C., Caulfield, Thomas R., Hudec, Roman, Ando, Maya, Truban, Dominika, Hou, Xu, Ogaki, Kotaro, Heckman, Michael G., James, Elle D., Swanberg, Maria, Jimenez-Ferrer, Itzia, Hansson, Oskar, Opala, Grzegorz, Siuda, Joanna, Boczarska-Jedynak, Magdalena, Friedman, Andrzej, Koziorowski, Dariusz, Aasly, Jan O., Lynch, Timothy, Mellick, George D., Mohan, Megha, Silburn, Peter A., Sanotsky, Yanosh, Vilariño-Güell, Carles, Farrer, Matthew J., Chen, Li, Dawson, Valina L., Dawson, Ted M., Wszolek, Zbigniew K., Ross, Owen A., and Springer, Wolfdieter
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- 2017
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21. Association of Essential Tremor With Novel Risk Loci
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Liao, Calwing, Castonguay, Charles-Etienne, Heilbron, Karl, Vuokila, Veikko, Medeiros, Miranda, Houle, Gabrielle, Akçimen, Fulya, Ross, Jay P., Catoire, Helene, Diez-Fairen, Monica, Kang, Jooeun, Mueller, Stefanie H., Girard, Simon L., Hopfner, Franziska, Lorenz, Delia, Clark, Lorraine N., Soto-Beasley, Alexandra I., Klebe, Stephan, Hallett, Mark, Wszolek, Zbigniew K., Pendziwiat, Manuela, Lorenzo-Betancor, Oswaldo, Seppi, Klaus, Berg, Daniela, Vilariño-Güell, Carles, Postuma, Ronald B., Bernard, Geneviève, Dupré, Nicolas, Jankovic, Joseph, Testa, Claudia M., Ross, Owen A., Arzberger, Thomas, Chouinard, Sylvain, Louis, Elan D., Mandich, Paola, Vitale, Carmine, Barone, Paolo, García-Martín, Elena, Alonso-Navarro, Hortensia, Agúndez, José A. G., Jiménez-Jiménez, Félix Javier, Pastor, Pau, Rajput, Alex, Deuschl, Günther, Kuhlenbaümer, Gregor, Meijer, Inge A., Dion, Patrick A., and Rouleau, Guy A.
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Research ,Online First ,Comments ,Original Investigation - Abstract
Key Points Question Can common genetic variants associated with essential tremor (ET) be identified? Findings In this genome-wide association study and meta-analysis including genetic data on 483 054 individuals, 5 genome-wide significant loci were associated with risk of ET and common variants were associated with approximately 18% of ET heritability. Meaning Findings of this study may help identify new genes and inform ET biology., This genome-wide association study identifies common variants associated with risk of essential tremor., Importance Essential tremor (ET) is one of the most common movement disorders, affecting 5% of the general population older than 65 years. Common variants are thought to contribute toward susceptibility to ET, but no variants have been robustly identified. Objective To identify common genetic factors associated with risk of ET. Design, Setting, and Participants Case-control genome-wide association study. Inverse-variance meta-analysis was used to combine cohorts. Multicenter samples collected from European populations were collected from January 2010 to September 2019 as part of an ongoing study. Included patients were clinically diagnosed with or reported having ET. Control individuals were not diagnosed with or reported to have ET. Of 485 250 individuals, data for 483 054 passed data quality control and were used. Main Outcomes and Measures Genotypes of common variants associated with risk of ET. Results Of the 483 054 individuals included, there were 7177 with ET (3693 [51.46%] female; mean [SD] age, 62.66 [15.12] years), and 475 877 control individuals (253 785 [53.33%] female; mean [SD] age, 56.40 [17.6] years). Five independent genome-wide significant loci and were identified and were associated with approximately 18% of ET heritability. Functional analyses found significant enrichment in the cerebellar hemisphere, cerebellum, and axonogenesis pathways. Genetic correlation (r), which measures the degree of genetic overlap, revealed significant common variant overlap with Parkinson disease (r, 0.28; P = 2.38 × 10−8) and depression (r, 0.12; P = 9.78 × 10−4). A separate fine-mapping of transcriptome-wide association hits identified genes such as BACE2, LRRN2, DHRS13, and LINC00323 in disease-relevant brain regions, such as the cerebellum. Conclusions and Relevance The results of this genome-wide association study suggest that a portion of ET heritability can be explained by common genetic variation and can help identify new common genetic risk factors for ET.
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- 2022
22. Elevated levels of serum CD5 antigen-like protein distinguish secondary progressive multiple sclerosis from other disease subtypes
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Kamma, Emily, primary, Becquart, Pierre, additional, Traboulsee, Anthony, additional, Schabas, Alice, additional, Vavasour, Irene M., additional, Laule, Cornelia, additional, Vilariño-Güell, Carles, additional, and Quandt, Jacqueline A., additional
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- 2021
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23. Defining neurodegeneration on Guam by targeted genomic sequencing
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Steele, John C., Guella, Ilaria, Szu-Tu, Chelsea, Lin, Michelle K., Thompson, Christina, Evans, Daniel M., Sherman, Holly E., Vilariño-Güell, Carles, Gwinn, Katrina, Morris, Huw, Dickson, Dennis W., and Farrer, Matthew J.
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- 2015
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24. Dnajc13 Genetic Variants in Parkinsonism
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Gustavsson, Emil K., Trinh, Joanne, Guella, Ilaria, Vilariño-Güell, Carles, Appel-Cresswell, Silke, Stoessl, Jon A., Tsui, Joseph K, McKeown, Martin, Rajput, Alex, Rajput, Ali H., Aasly, Jan O., and Farrer, Matthew J.
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- 2015
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25. Clinical, positron emission tomography, and pathological studies of DNAJC13 p.N855S Parkinsonism
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Appel-Cresswell, Silke, Rajput, Ali H, Sossi, Vesna, Thompson, Christina, Silva, Vanessa, McKenzie, Jessamyn, Dinelle, Katherine, McCormick, Siobhan E., Vilariño-Güell, Carles, Stoessl, Jon A., Dickson, Dennis W, Robinson, Chris A., Farrer, Matthew J., and Rajput, Alex
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- 2014
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26. Exome-wide rare variant analysis in familial essential tremor
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Diez-Fairen, Monica, Houle, Gabrielle, Ortega-Cubero, Sara, Bandres-Ciga, Sara, Alvarez, Ignacio, Carcel, Maria, Ibañez, Laura, Fernandez, Maria Victoria, Budde, John P, Trotta, Jean-Rémi, Tonda, Raúl, Chong, Jessica X, Bamshad, Michael J, Nickerson, Deborah A, University of Washington Center for Mendelian Genomics (UWCMG), Aguilar, Miquel, Tartari, Juan P, Gironell, Alexandre, García-Martín, Elena, Agundez, Jose Ag, Alonso-Navarro, Hortensia, Jimenez-Jimenez, Felix Javier, Fernandez, Manel, Valldeoriola, Francesc, Marti, Maria Jose, Tolosa, Eduard, Coria, Francisco, Pastor, Maria A, Vilariño-Güell, Carles, Rajput, Alex, Dion, Patrick A, Cruchaga, Carlos, Rouleau, Guy A, and Pastor, Pau
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0301 basic medicine ,Adult ,Male ,Candidate gene ,Movement disorders ,Essential Tremor ,Disease ,Biology ,Article ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Matrix Metalloproteinase 10 ,Exome Sequencing ,medicine ,Humans ,Genetic Predisposition to Disease ,Age of Onset ,Gene ,Exome ,Exome sequencing ,Aged ,Genetics ,Genetic risk ,Aged, 80 and over ,Essential tremor ,MMP10 ,Rare variants ,Heritability ,Middle Aged ,medicine.disease ,Pedigree ,030104 developmental biology ,Neurology ,WES ,Female ,Neurology (clinical) ,Geriatrics and Gerontology ,medicine.symptom ,030217 neurology & neurosurgery - Abstract
Introduction Essential tremor (ET) is one of the most common movement disorders. Despite its high prevalence and heritability, its genetic etiology remains elusive with only a few susceptibility genes identified and poorly replicated. Our aim was to find novel candidate genes involved in ET predisposition through whole exome sequencing. Methods We studied eight multigenerational families (N = 40 individuals) with an autosomal-dominant inheritance using a comprehensive strategy combining whole exome sequencing followed by case-control association testing of prioritized variants in a separate cohort comprising 521 ET cases and 596 controls. We further performed gene-based burden analyses in an additional dataset comprising 789 ET patients and 770 healthy individuals to investigate whether there was an enrichment of rare deleterious variants within our candidate genes. Results Fifteen variants co-segregated with disease status in at least one of the families, among which rs749875462 in CCDC183, rs535864157 in MMP10 and rs114285050 in GPR151 showed a nominal association with ET. However, we found no significant enrichment of rare variants within these genes in cases compared with controls. Interestingly, MMP10 protein is involved in the inflammatory response to neuronal damage and has been previously associated with other neurological disorders. Conclusions We prioritized a set of promising genes, especially MMP10, for further genetic and functional studies in ET. Our study suggests that rare deleterious coding variants that markedly increase susceptibility to ET are likely to be found in many genes. Future studies are needed to replicate and further infer biological mechanisms and potential disease causality for our identified genes.
- Published
- 2020
27. Transcriptome analysis of the NR1H3 mouse model of multiple sclerosis reveals a pro-inflammatory phenotype with dysregulation of lipid metabolism and immune response genes
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Vilariño-Güell, Carles, primary, Encarnacion, Mary, additional, Bernales, Cecily Q, additional, Kamma, Emily, additional, Becquart, Pierre, additional, and Quandt, Jacqueline A, additional
- Published
- 2021
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28. Enhanced expression of complement and microglial-specific genes prior to clinical progression in the MOG-experimental autoimmune encephalomyelitis model of multiple sclerosis
- Author
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Becquart, Pierre, primary, Vilariño-Güell, Carles, additional, and Quandt, Jacqueline A., additional
- Published
- 2020
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29. A commentary on fine mapping and resequencing of the PARK16 locus in Parkinson’s disease
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Trinh, Joanne, Vilariño-Güell, Carles, and Ross, Owen A
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- 2015
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30. Exome sequencing in multiple sclerosis families identifies 12 candidate genes and nominates biological pathways for the genesis of disease
- Author
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Neurociencias, Bioquímica y biología molecular, Neurozientziak, Biokimika eta biologia molekularra, Vilariño Güell, Carles, Zimprich, Alexander, Martinelli Boneschi, Filippo, Herculano, Bruno, Wang, Zhe, Matesanz, Fuencisla, Urcelay, Elena, Vandenbroeck, Koen, Leyva, Laura, Gris, Denis, Massaad, Charbel, Quandt, Jacqueline A., Traboulsee, Anthony L., Encarnacion, Mary, Bernales, Cecily Q., Follett, Jordan, Yee, Irene M., Criscuoli, Maria G., Deutschlander, Angela, Reinthaler, Eva M., Zrzavy, Tobias, Mascia, Elisabetta, Zauli, Andrea, Esposito, Federica, Alcina, Antonio, Izquierdo, Guillermo, Espino Paisan, Laura, Mena Lucía, Jorge, Rodríguez-Antigüedad Zarranz, Alfredo, Urbaneja Romero, Patricia, Ortega Pinazo, Jesús, Song, Weihong, Sadovnick, A. Dessa, Neurociencias, Bioquímica y biología molecular, Neurozientziak, Biokimika eta biologia molekularra, Vilariño Güell, Carles, Zimprich, Alexander, Martinelli Boneschi, Filippo, Herculano, Bruno, Wang, Zhe, Matesanz, Fuencisla, Urcelay, Elena, Vandenbroeck, Koen, Leyva, Laura, Gris, Denis, Massaad, Charbel, Quandt, Jacqueline A., Traboulsee, Anthony L., Encarnacion, Mary, Bernales, Cecily Q., Follett, Jordan, Yee, Irene M., Criscuoli, Maria G., Deutschlander, Angela, Reinthaler, Eva M., Zrzavy, Tobias, Mascia, Elisabetta, Zauli, Andrea, Esposito, Federica, Alcina, Antonio, Izquierdo, Guillermo, Espino Paisan, Laura, Mena Lucía, Jorge, Rodríguez-Antigüedad Zarranz, Alfredo, Urbaneja Romero, Patricia, Ortega Pinazo, Jesús, Song, Weihong, and Sadovnick, A. Dessa
- Abstract
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system characterized by myelin loss and neuronal dysfunction. Although the majority of patients do not present familial aggregation, Mendelian forms have been described. We performed whole-exome sequencing analysis in 132 patients from 34 multi-incident families, which nominated likely pathogenic variants for MS in 12 genes of the innate immune system that regulate the transcription and activation of inflammatory mediators. Rare missense or nonsense variants were identified in genes of the fibrinolysis and complement pathways (PLAU, MASP1, C2), inflammasome assembly (NLRP12), Wnt signaling (UBR2, CTNNA3, NFATC2, RNF213), nuclear receptor complexes (NCOA3), and cation channels and exchangers (KCNG4, SLC24A6, SLC8B1). These genes suggest a disruption of interconnected immunological and pro-inflammatory pathways as the initial event in the pathophysiology of familial MS, and provide the molecular and biological rationale for the chronic inflammation, demyelination and neurodegeneration observed in MS patients. Author summary Although the majority of patients diagnosed with multiple sclerosis do not have a family history of disease, 13% report having a close relative also diagnosed with multiple sclerosis. In these families, the cause of multiple sclerosis can be largely attributed to a single genetic variant that is transmitted through generations. In this study we analyzed DNA from 132 patients from 34 families, resulting in the identification of 12 rare genetic variants that are largely responsible for the onset of multiple sclerosis in these families. These variants are located in genes implicated in specific immunological pathways, and suggest the biological mechanisms that trigger the onset of multiple sclerosis. These genes and variants provide the means for the generation of cellular and animal models of human disease, and highlight biological targets for the development of novel treatment
- Published
- 2019
31. Exome sequencing study in patients with multiple sclerosis reveals variants associated with disease course
- Author
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Gil Varea, Elia, Urcelay, Elena, Vilariño-Güell, Carles, Costa, Carme, Midaglia, Luciana, Matesanz, Fuencisla, Rodríguez-Antigüedad, Alfredo, Oksenberg, Jorge, Espino-Paisan, Laura, Dessa Sadovnick, A., Saiz, Albert, Villar, Luisa M., García-Merino, Juan Antonio, Ramió-Torrentà, Lluís, Triviño, Juan Carlos, Quintana, Ester, Robles, René, Sánchez-López, Antonio, Arroyo, Rafael, Alvarez-Cermeño, José C, Vidal-Jordana, Angela, Malhotra, Sunny, Fissolo, Nicolás, Montalban, Xavier, Comabella, Manuel, Universitat Autònoma de Barcelona, Instituto de Salud Carlos III, Junta de Andalucía, Ministerio de Economía y Competitividad (España), Society of Canada Scientific Research Foundation, European Commission, and Canadian Institutes of Health Research
- Subjects
Male ,0301 basic medicine ,Oncology ,Exome sequencing ,Carboxypeptidases A ,Messenger ,Esclerosi múltiple ,Disease ,Neurodegenerative ,lcsh:RC346-429 ,Whole Exome Sequencing ,Cohort Studies ,Gene Frequency ,2.1 Biological and endogenous factors ,Immunologia ,Aetiology ,IGSF9B ,Disease course ,screening and diagnosis ,CPXM2 ,General Neuroscience ,Brain ,Single Nucleotide ,Fenotip ,Detection ,Phenotype ,Neurology ,Neurological ,Cohort ,Disease Progression ,Female ,4.2 Evaluation of markers and technologies ,medicine.medical_specialty ,Genotype ,Clinical Sciences ,Immunology ,Immunoglobulins ,NLRP9 ,Nerve Tissue Proteins ,Single-nucleotide polymorphism ,Autoimmune Disease ,Polymorphism, Single Nucleotide ,Multiple sclerosis ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Clinical Research ,Internal medicine ,Genetics ,medicine ,Humans ,SNP ,Genetic Predisposition to Disease ,RNA, Messenger ,Polymorphism ,Genotyping ,Allele frequency ,lcsh:Neurology. Diseases of the nervous system ,Neurology & Neurosurgery ,business.industry ,Human Genome ,Neurosciences ,medicine.disease ,Brain Disorders ,030104 developmental biology ,RNA ,business ,Polymorphisms - Abstract
[Background]: It remains unclear whether disease course in multiple sclerosis (MS) is influenced by genetic polymorphisms. Here, we aimed to identify genetic variants associated with benign and aggressive disease courses in MS patients., [Methods]: MS patients were classified into benign and aggressive phenotypes according to clinical criteria. We performed exome sequencing in a discovery cohort, which included 20 MS patients, 10 with benign and 10 with aggressive disease course, and genotyping in 2 independent validation cohorts. The first validation cohort encompassed 194 MS patients, 107 with benign and 87 with aggressive phenotypes. The second validation cohort comprised 257 patients, of whom 224 patients had benign phenotypes and 33 aggressive disease courses. Brain immunohistochemistries were performed using disease course associated genes antibodies., [Results]: By means of single-nucleotide polymorphism (SNP) detection and comparison of allele frequencies between patients with benign and aggressive phenotypes, a total of 16 SNPs were selected for validation from the exome sequencing data in the discovery cohort. Meta-analysis of genotyping results in two validation cohorts revealed two polymorphisms, rs28469012 and rs10894768, significantly associated with disease course. SNP rs28469012 is located in CPXM2 (carboxypeptidase X, M14 family, member 2) and was associated with aggressive disease course (uncorrected p value, [Conclusions]: Genetic variants located in CPXM2, IGSF9B, and NLRP9 have the potential to modulate disease course in MS patients and may be used as disease activity biomarkers to identify patients with divergent disease courses. Altogether, the reported results from this study support the influence of genetic factors in MS disease course and may help to better understand the complex molecular mechanisms underlying disease pathogenesis., This work was supported by (a) grants PI10/02099, FIS PI13/0879, PI15/00513, PI15/00587, PI16/01259, RD16/0015/0001, RD16/0015/0002, RD16/0015/0004 integrated in the Plan Estatal de Investigación Científica y Técnica de Innovación I+D+I and co-funded by the Instituto de Salud Carlos IIISubdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER), and Red Española de Esclerosis Múltiple (REEM); (b) Junta de Andalucía (JA)-FEDER grant CTS2704, Ministerio de Economía y Competitividad (grant number SAF 2016-80595-C2-1-P); (c) MS Society of Canada Scientific Research Foundation as part of the CCPGSMS, and research undertaken thanks to funding from the Canada Research Chair (950-228408) program, Michael Smith Foundation for Health Research (16827) and Canadian Institutes of Health Research (MOP-137051).
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- 2018
32. Additional file 1: of Exome sequencing study in patients with multiple sclerosis reveals variants associated with disease course
- Author
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Gil-Varea, Elia, Urcelay, Elena, Vilariño-Güell, Carles, Costa, Carme, Midaglia, Luciana, Matesanz, Fuencisla, Rodríguez-Antigüedad, Alfredo, Oksenberg, Jorge, Espino-Paisan, Laura, A. Dessa Sadovnick, Saiz, Albert, Villar, Luisa, García-Merino, Juan, Lluís Ramió-Torrentà, Triviño, Juan, Quintana, Ester, Robles, René, Sánchez-López, Antonio, Arroyo, Rafael, Alvarez-Cermeño, Jose, Vidal-Jordana, Angela, Malhotra, Sunny, Fissolo, Nicolas, Montalban, Xavier, and Comabella, Manuel
- Abstract
Table S1. Demographic and clinical characteristics of the MS patients with benign and aggressive disease courses. Figure S1. IGSF9B expression levels in PBMC from MS patients stratified according to the genetic variant associated with disease course. Figure S2. GTEx eQTLs of rs10894768 associations with IGSF9B expression in thyroid and pancreas tissues. (DOC 551 kb)
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- 2018
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33. MSJ803789_supplementary_data – Supplemental material for Analysis of Canadian multiple sclerosis patients does not support a role for FKBP6 in disease
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Vilariño-Güell, Carles, Encarnacion, Mary, Bernales, Cecily Q, and A Dessa Sadovnick
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FOS: Clinical medicine ,111702 Aged Health Care ,FOS: Health sciences ,110904 Neurology and Neuromuscular Diseases - Abstract
Supplemental material, MSJ803789_supplementary_data for Analysis of Canadian multiple sclerosis patients does not support a role for FKBP6 in disease by Carles Vilariño-Güell, Mary Encarnacion, Cecily Q Bernales and A Dessa Sadovnick in Multiple Sclerosis Journal
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- 2018
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34. NLRX1 inhibits the early stages of CNS inflammation and prevents the onset of spontaneous autoimmunity
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Gharagozloo, Marjan, primary, Mahmoud, Shaimaa, additional, Simard, Camille, additional, Yamamoto, Kenzo, additional, Bobbala, Diwakar, additional, Ilangumaran, Subburaj, additional, Smith, Matthew D., additional, Lamontagne, Albert, additional, Jarjoura, Samir, additional, Denault, Jean-Bernard, additional, Blais, Véronique, additional, Gendron, Louis, additional, Vilariño-Güell, Carles, additional, Sadovnick, A. Dessa, additional, Ting, Jenny P., additional, Calabresi, Peter A., additional, Amrani, Abdelaziz, additional, and Gris, Denis, additional
- Published
- 2019
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35. Exome sequencing in multiple sclerosis families identifies 12 candidate genes and nominates biological pathways for the genesis of disease
- Author
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Vilariño-Güell, Carles, primary, Zimprich, Alexander, additional, Martinelli-Boneschi, Filippo, additional, Herculano, Bruno, additional, Wang, Zhe, additional, Matesanz, Fuencisla, additional, Urcelay, Elena, additional, Vandenbroeck, Koen, additional, Leyva, Laura, additional, Gris, Denis, additional, Massaad, Charbel, additional, Quandt, Jacqueline A., additional, Traboulsee, Anthony L., additional, Encarnacion, Mary, additional, Bernales, Cecily Q., additional, Follett, Jordan, additional, Yee, Irene M., additional, Criscuoli, Maria G., additional, Deutschländer, Angela, additional, Reinthaler, Eva M., additional, Zrzavy, Tobias, additional, Mascia, Elisabetta, additional, Zauli, Andrea, additional, Esposito, Federica, additional, Alcina, Antonio, additional, Izquierdo, Guillermo, additional, Espino-Paisán, Laura, additional, Mena, Jorge, additional, Antigüedad, Alfredo, additional, Urbaneja-Romero, Patricia, additional, Ortega-Pinazo, Jesús, additional, Song, Weihong, additional, and Sadovnick, A. Dessa, additional
- Published
- 2019
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36. Exome sequencing study in patients with multiple sclerosis reveals variants associated with disease course
- Author
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Instituto de Salud Carlos III, Junta de Andalucía, Ministerio de Economía y Competitividad (España), Society of Canada Scientific Research Foundation, European Commission, Canadian Institutes of Health Research, Gil-Varea, Elia, Urcelay, Elena, Vilariño-Güell, Carles, Costa, Carme, Midaglia, Luciana, Matesanz, F., Rodríguez-Antigüedad, Alfredo, Oksenberg, J. R., Espino-Paisan, Laura, Dessa Sadovnick, A., Sáiz, Albert, Villar, Luisa M., García-Merino, Juan A, Ramió-Torrentà, Lluís, Triviño, Juan C., Quintana, Ester, Robles, René, Sánchez-López, Antonio, Arroyo, Rafael, Álvarez-Cermeño, José Carlos, Vidal-Jordana, Angela, Malhotra, Sunny, Fissolo, Nicolas, Montalbán, Xavier, Comabella, Manuel, Instituto de Salud Carlos III, Junta de Andalucía, Ministerio de Economía y Competitividad (España), Society of Canada Scientific Research Foundation, European Commission, Canadian Institutes of Health Research, Gil-Varea, Elia, Urcelay, Elena, Vilariño-Güell, Carles, Costa, Carme, Midaglia, Luciana, Matesanz, F., Rodríguez-Antigüedad, Alfredo, Oksenberg, J. R., Espino-Paisan, Laura, Dessa Sadovnick, A., Sáiz, Albert, Villar, Luisa M., García-Merino, Juan A, Ramió-Torrentà, Lluís, Triviño, Juan C., Quintana, Ester, Robles, René, Sánchez-López, Antonio, Arroyo, Rafael, Álvarez-Cermeño, José Carlos, Vidal-Jordana, Angela, Malhotra, Sunny, Fissolo, Nicolas, Montalbán, Xavier, and Comabella, Manuel
- Abstract
[Background]: It remains unclear whether disease course in multiple sclerosis (MS) is influenced by genetic polymorphisms. Here, we aimed to identify genetic variants associated with benign and aggressive disease courses in MS patients., [Methods]: MS patients were classified into benign and aggressive phenotypes according to clinical criteria. We performed exome sequencing in a discovery cohort, which included 20 MS patients, 10 with benign and 10 with aggressive disease course, and genotyping in 2 independent validation cohorts. The first validation cohort encompassed 194 MS patients, 107 with benign and 87 with aggressive phenotypes. The second validation cohort comprised 257 patients, of whom 224 patients had benign phenotypes and 33 aggressive disease courses. Brain immunohistochemistries were performed using disease course associated genes antibodies., [Results]: By means of single-nucleotide polymorphism (SNP) detection and comparison of allele frequencies between patients with benign and aggressive phenotypes, a total of 16 SNPs were selected for validation from the exome sequencing data in the discovery cohort. Meta-analysis of genotyping results in two validation cohorts revealed two polymorphisms, rs28469012 and rs10894768, significantly associated with disease course. SNP rs28469012 is located in CPXM2 (carboxypeptidase X, M14 family, member 2) and was associated with aggressive disease course (uncorrected p value < 0.05). SNP rs10894768, which is positioned in IGSF9B (immunoglobulin superfamily member 9B) was associated with benign phenotype (uncorrected p value < 0.05). In addition, a trend for association with benign phenotype was observed for a third SNP, rs10423927, in NLRP9 (NLR family pyrin domain containing 9). Brain immunohistochemistries in chronic active lesions from MS patients revealed expression of IGSF9B in astrocytes and macrophages/microglial cells, and expression of CPXM2 and NLRP9 restricted to brain macrophages/microglia., [Conclusions]: Genetic variants located in CPXM2, IGSF9B, and NLRP9 have the potential to modulate disease course in MS patients and may be used as disease activity biomarkers to identify patients with divergent disease courses. Altogether, the reported results from this study support the influence of genetic factors in MS disease course and may help to better understand the complex molecular mechanisms underlying disease pathogenesis.
- Published
- 2018
37. The Role of Rare Coding Variants in Parkinson's Disease GWAS Loci.
- Author
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Germer, Elisabeth Luisa, Imhoff, Sophie, Vilariño-Güell, Carles, Kasten, Meike, Seibler, Philip, Brüggemann, Norbert, Klein, Christine, and Trinh, Joanne
- Subjects
PARKINSON'S disease ,GENETIC testing ,DATA replication ,GENE frequency - Abstract
Introduction: Genome-wide association studies (GWAS) have identified multiple loci associated with Parkinson's disease (PD) risk. The presence of rare variants within these loci that may account for the increased susceptibility requires further investigation. Methods: Using exome sequencing, we performed a comprehensive rare variant screen of genes located within 56 novel PD loci. We first analyzed exomes from 109 subjects in the discovery cohort (85 diagnosed with PD and 24 healthy controls) and filtered for rare coding variants with minor allele frequency <0.01 and combined annotation-dependent depletion > 15. Further investigation of exome data from a replication cohort of 2,859 European patients with PD (International Parkinson's Disease Genomics Consortium) and 24,146 non-Finnish European controls from gnomAD were used for association testing of specific rare variants found in the discovery cohort. Results: Our genetic screening identified 54 potential disease-relevant variants in 71 genes in 109 subjects. Six out of 54 variants were found in two or more patients and were not observed in healthy controls: DNAH1 p.A3639T, STAB1 p.S1089G, ANK2 p.V3634D, ANK2 p.R3906W, SH3GL2 p.G276V, and NOD2 p.G908R. Replication in the International Parkinson's Disease Genomics Consortium (IPDGC) confirmed the association with PD risk for three out of the six identified variants (STAB1 p.S1089G, SH3GL2 p.G276V, and NOD2 p.G908R) (p < 10
−3 ). Conclusion: Our study suggests that some of the associations identified in PD risk loci can be ascribed to rare variants with likely functional effects that modify PD risk. [ABSTRACT FROM AUTHOR]- Published
- 2019
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38. Analysis of CH25H in multiple sclerosis and neuromyelitis optica
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Forwell, Amanda L., Bernales, Cecily Q., Ross, Jay P., Yee, Irene M., Encarnacion, Mary, Lee, Joshua D., Sadovnick, A. Dessa, Traboulsee, Anthony L., and Vilariño-Güell, Carles
- Published
- 2016
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39. Absence of Mutation Enrichment for Genes Phylogenetically Conserved in the Olivocerebellar Motor Circuitry in a Cohort of Canadian Essential Tremor Cases
- Author
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Schmouth, Jean-François, primary, Houle, Gabrielle, additional, Ambalavanan, Amirthagowri, additional, Leblond, Claire S., additional, Spiegelman, Dan, additional, Laurent, Sandra B., additional, Bourassa, Cynthia V., additional, Panisset, Michel, additional, Chouinard, Sylvain, additional, Dupré, Nicolas, additional, Vilariño-Güell, Carles, additional, Rajput, Alex, additional, Dion, Patrick A., additional, and Rouleau, Guy A., additional
- Published
- 2018
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40. Analysis of Canadian multiple sclerosis patients does not support a role for FKBP6 in disease
- Author
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Vilariño-Güell, Carles, primary, Encarnacion, Mary, additional, Bernales, Cecily Q, additional, and Sadovnick, A Dessa, additional
- Published
- 2018
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41. Whole-Exome Sequencing of an Exceptional Longevity Cohort
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Nygaard, Haakon B, primary, Erson-Omay, E Zeynep, additional, Wu, Xiujuan, additional, Kent, Brianne A, additional, Bernales, Cecily Q, additional, Evans, Daniel M, additional, Farrer, Matthew J, additional, Vilariño-Güell, Carles, additional, and Strittmatter, Stephen M, additional
- Published
- 2018
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42. Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients
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Dessa Sadovnick, A., Alcina, Antonio, Fedetz, María, Matesanz, F., and Vilariño-Güell, Carles
- Abstract
Dessa Sadovnick, A.; Alcina, Antonio; Fedetz, María; Matesanz, F.; Vilariño-Güell, Carles; Dessa Sadovnick, A. et. al., Multiple sclerosis (MS) is a prevalent neurological disease of complex etiology. Here, we describe the characterization of a multi-incident MS family that nominated a rare missense variant (p.G420D) in plasminogen (PLG) as a putative genetic risk factor for MS. Genotyping of PLG p.G420D (rs139071351) in 2160 MS patients, and 886 controls from Canada, identified 10 additional probands, two sporadic patients and one control with the variant. Segregation in families harboring the rs139071351 variant, identified p.G420D in 26 out of 30 family members diagnosed with MS, 14 unaffected parents, and 12 out of 30 family members not diagnosed with disease. Despite considerably reduced penetrance, linkage analysis supports cosegregation of PLG p.G420D and disease. Genotyping of PLG p.G420D in 14446 patients, and 8797 controls from Canada, France, Spain, Germany, Belgium, and Austria failed to identify significant association with disease (P = 0.117), despite an overall higher prevalence in patients (OR = 1.32; 95% CI = 0.93–1.87). To assess whether additional rare variants have an effect on MS risk, we sequenced PLG in 293 probands, and genotyped all rare variants in cases and controls. This analysis identified nine rare missense variants, and although three of them were exclusively observed in MS patients, segregation does not support pathogenicity. PLG is a plausible biological candidate for MS owing to its involvement in immune system response, blood-brain barrier permeability, and myelin degradation. Moreover, components of its activation cascade have been shown to present increased activity or expression in MS patients compared to controls; further studies are needed to clarify whether PLG is involved in MS susceptibility., We also thank Généthon, L’Association Française contre les Myopathies (AFM), la Fondation pour l’Aide à la Recherche sur la Sclérose en Plaques (ARSEP), and the Biological Resources Centre (BRC) of The French Multiple Sclerosis Genetics Group (CRB-REFGENSEP). This research was undertaken thanks to funding from the Canada Research Chair [950-228408] and Canada Excellence Research Chair programs [214444], Canadian Institutes of Health Research [MOP-137051], Vancouver Coastal Health Research Institute, the Milan & Maureen Ilich Foundation [11-32095000], and the Vancouver Foundation [ADV14-1597]. Replication studies received funding from the program “Investissements d’avenir” ANR-10-IAIHU-06. Fondo de Investigación Sanitaria (FIS)-Instituto de Salud Carlos III (ISCIII)-Fondos Europeos de Desarrollo Regional (FEDER), Unión Europea [grant numbers P12/00555, PI13/01527, PI13/01466 and PI13/0879 to F.M., A.A. and G.I.] and Junta de Andalucía -FEDER [grant number CTS2704 to F.M.]. B.D. is a Clinical Investigator of the Research Foundation Flanders (FWO-Vlaanderen). A.G. and B.D. are supported by the Research Fund KU Leuven (OT/11/087 and CREA/14/023) and the Research Foundation Flanders (G073415N). A.L.T. reports personal fees from Biogen Idec, Chugai, Medimmune, Teva Innovation, and EMD Serono, and grants and personal fees from Genzyme Sanofi and Roche.
- Published
- 2016
43. Analysis of NOD-like receptor NLRP1 in multiple sclerosis families
- Author
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Bernales, Cecily Q., primary, Encarnacion, Mary, additional, Criscuoli, Maria G., additional, Yee, Irene M., additional, Traboulsee, Anthony L., additional, Sadovnick, A. Dessa, additional, and Vilariño-Güell, Carles, additional
- Published
- 2017
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44. Purinergic receptorsP2RX4andP2RX7in familial multiple sclerosis
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Sadovnick, A Dessa, primary, Gu, Ben J, additional, Traboulsee, Anthony L, additional, Bernales, Cecily Q, additional, Encarnacion, Mary, additional, Yee, Irene M, additional, Criscuoli, Maria G, additional, Huang, Xin, additional, Ou, Amber, additional, Milligan, Carol J, additional, Petrou, Steven, additional, Wiley, James S, additional, and Vilariño-Güell, Carles, additional
- Published
- 2017
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45. Reply: Heterozygous PINK1 p.G411S in rapid eye movement sleep behaviour disorder
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Puschmann, Andreas, primary, Fiesel, Fabienne C., additional, Caulfield, Thomas R., additional, Hudec, Roman, additional, Ando, Maya, additional, Truban, Dominika, additional, Hou, Xu, additional, Ogaki, Kotaro, additional, Heckman, Michael G., additional, James, Elle D., additional, Swanberg, Maria, additional, Jimenez-Ferrer, Itzia, additional, Hansson, Oskar, additional, Opala, Grzegorz, additional, Siuda, Joanna, additional, Boczarska-Jedynak, Magdalena, additional, Friedman, Andrzej, additional, Koziorowski, Dariusz, additional, Rudzińska-Bar, Monika, additional, Aasly, Jan O., additional, Lynch, Timothy, additional, Mellick, George D., additional, Mohan, Megha, additional, Silburn, Peter A., additional, Sanotsky, Yanosh, additional, Vilariño-Güell, Carles, additional, Farrer, Matthew J., additional, Chen, Li, additional, Dawson, Valina L., additional, Dawson, Ted M., additional, Wszolek, Zbigniew K., additional, Ross, Owen A., additional, and Springer, Wolfdieter, additional
- Published
- 2017
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46. Heterozygous PINK1 p.G411S increases risk of Parkinson’s disease via a dominant-negative mechanism
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Puschmann, Andreas, primary, Fiesel, Fabienne C., additional, Caulfield, Thomas R., additional, Hudec, Roman, additional, Ando, Maya, additional, Truban, Dominika, additional, Hou, Xu, additional, Ogaki, Kotaro, additional, Heckman, Michael G., additional, James, Elle D., additional, Swanberg, Maria, additional, Jimenez-Ferrer, Itzia, additional, Hansson, Oskar, additional, Opala, Grzegorz, additional, Siuda, Joanna, additional, Boczarska-Jedynak, Magdalena, additional, Friedman, Andrzej, additional, Koziorowski, Dariusz, additional, Aasly, Jan O., additional, Lynch, Timothy, additional, Mellick, George D., additional, Mohan, Megha, additional, Silburn, Peter A., additional, Sanotsky, Yanosh, additional, Vilariño-Güell, Carles, additional, Farrer, Matthew J., additional, Chen, Li, additional, Dawson, Valina L., additional, Dawson, Ted M., additional, Wszolek, Zbigniew K., additional, Ross, Owen A., additional, and Springer, Wolfdieter, additional
- Published
- 2016
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47. DNM3 and genetic modifiers of age of onset in LRRK2 Gly2019Ser parkinsonism: a genome-wide linkage and association study
- Author
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Trinh, Joanne, primary, Gustavsson, Emil K, additional, Vilariño-Güell, Carles, additional, Bortnick, Stephanie, additional, Latourelle, Jeanne, additional, McKenzie, Marna B, additional, Tu, Chelsea Szu, additional, Nosova, Ekaterina, additional, Khinda, Jaskaran, additional, Milnerwood, Austen, additional, Lesage, Suzanne, additional, Brice, Alexis, additional, Tazir, Meriem, additional, Aasly, Jan O, additional, Parkkinen, Laura, additional, Haytural, Hazal, additional, Foroud, Tatiana, additional, Myers, Richard H, additional, Sassi, Samia Ben, additional, Hentati, Emna, additional, Nabli, Fatma, additional, Farhat, Emna, additional, Amouri, Rim, additional, Hentati, Fayçal, additional, and Farrer, Matthew J, additional
- Published
- 2016
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48. Whole-Exome Sequencing of an Exceptional Longevity Cohort.
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Nygaard, Haakon B, Erson-Omay, E Zeynep, Wu, Xiujuan, Kent, Brianne A, Bernales, Cecily Q, Evans, Daniel M, Farrer, Matthew J, Vilariño-Güell, Carles, and Strittmatter, Stephen M
- Subjects
LONGEVITY ,ALZHEIMER'S disease ,CENTENARIANS ,NEURODEGENERATION - Abstract
Centenarians represent a unique cohort to study the genetic basis for longevity and factors determining the risk of neurodegenerative disorders, including Alzheimer's disease (AD). The estimated genetic contribution to longevity is highest in centenarians and super-cententenarians, but few genetic variants have been shown to clearly impact this phenotype. While the genetic risk for AD and other dementias is now well understood, the frequency of known dementia risk variants in centenarians is not fully characterized. To address these questions, we performed whole-exome sequencing on 100 individuals of 98-108 years age in search of genes with large effect sizes towards the exceptional aging phenotype. Overall, we were unable to identify a rare protein-altering variant or individual genes with an increased burden of rare variants associated with exceptional longevity. Gene burden analysis revealed three genes of nominal statistical significance associated with extreme aging, including LYST, MDN1, and RBMXL1. Several genes with variants conferring an increased risk for AD and other dementias were identified, including TREM2, EPHA1, ABCA7, PLD3, MAPT, and NOTCH3. Larger centenarian studies will be required to further elucidate the genetic basis for longevity, and factors conferring protection against age-dependent neurodegenerative syndromes. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
49. Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients
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Medicina, Neurociencias, Medikuntza, Neurozientziak, Sadovnick, A. Dessa, Traboulsee, Anthony L., Bernales, Cecily Q., Ross, Jay P., Forwell, Amanda L., Yee, Irene M., Guillot-Noel, Lena, Fontaine, Bertrand, Cournu-Rebeix, Isabelle, Alcina, Antonio, Fedetz, María, Izquierdo, Guillermo, Matesanz, Fuencisla, Hilven, Kelly, Goris, An, Astobiza Pérez, Janire, Alloza Moral, Iraide, Rodríguez-Antigüedad Zarranz, Alfredo, Vandenbroeck, Koen, Akkad, Denis A., Aktas, Orhan, Blaschke, Paul, Buttmann, Mathias, Chan, Andrew, Epplen, Joerg T., Gerdes, Lisa-Ann, Kroner, Antje, Kubisch, Christian, Kümpfel, Tania, Lohse, Peter, Rieckmann, Peter, Zettl, Uwe K., Zipp, Frauke, Bertram, Lars, Lill, Christina M., Fernández, Óscar, Urbaneja, Patricia, Leyva, Laura, Alvarez-Cermeño, José Carlos, Arroyo, Rafael, Garagorri, Aroa M., García-Martínez, Angel, Villar, Luisa M., Urcelay, Elena, Malhotra, Sunny, Montalbán, Xavier, Comabella, Manuel, Berger, Thomas, Fazekas, Franz, Reindl, Markus, Schmied, Mascha C., Zimprich, Alexander, Vilariño-Güell, Carles, Medicina, Neurociencias, Medikuntza, Neurozientziak, Sadovnick, A. Dessa, Traboulsee, Anthony L., Bernales, Cecily Q., Ross, Jay P., Forwell, Amanda L., Yee, Irene M., Guillot-Noel, Lena, Fontaine, Bertrand, Cournu-Rebeix, Isabelle, Alcina, Antonio, Fedetz, María, Izquierdo, Guillermo, Matesanz, Fuencisla, Hilven, Kelly, Goris, An, Astobiza Pérez, Janire, Alloza Moral, Iraide, Rodríguez-Antigüedad Zarranz, Alfredo, Vandenbroeck, Koen, Akkad, Denis A., Aktas, Orhan, Blaschke, Paul, Buttmann, Mathias, Chan, Andrew, Epplen, Joerg T., Gerdes, Lisa-Ann, Kroner, Antje, Kubisch, Christian, Kümpfel, Tania, Lohse, Peter, Rieckmann, Peter, Zettl, Uwe K., Zipp, Frauke, Bertram, Lars, Lill, Christina M., Fernández, Óscar, Urbaneja, Patricia, Leyva, Laura, Alvarez-Cermeño, José Carlos, Arroyo, Rafael, Garagorri, Aroa M., García-Martínez, Angel, Villar, Luisa M., Urcelay, Elena, Malhotra, Sunny, Montalbán, Xavier, Comabella, Manuel, Berger, Thomas, Fazekas, Franz, Reindl, Markus, Schmied, Mascha C., Zimprich, Alexander, and Vilariño-Güell, Carles
- Abstract
Multiple sclerosis (MS) is a prevalent neurological disease of complex etiology. Here, we describe the characterization of a multi-incident MS family that nominated a rare missense variant (p.G420D) in plasminogen (PLG) as a putative genetic risk factor for MS. Genotyping of PLG p.G420D (rs139071351) in 2160 MS patients, and 886 controls from Canada, identified 10 additional probands, two sporadic patients and one control with the variant. Segregation in families harboring the rs139071351 variant, identified p.G420D in 26 out of 30 family members diagnosed with MS, 14 unaffected parents, and 12 out of 30 family members not diagnosed with disease. Despite considerably reduced penetrance, linkage analysis supports cosegregation of PLG p.G420D and disease. Genotyping of PLG p. G420D in 14446 patients, and 8797 controls from Canada, France, Spain, Germany, Belgium, and Austria failed to identify significant association with disease (P = 0.117), despite an overall higher prevalence in patients (OR = 1.32; 95% CI = 0.931.87). To assess whether additional rare variants have an effect on MS risk, we sequenced PLG in 293 probands, and genotyped all rare variants in cases and controls. This analysis identified nine rare missense variants, and although three of them were exclusively observed in MS patients, segregation does not support pathogenicity. PLG is a plausible biological candidate for MS owing to its involvement in immune system response, blood-brain barrier permeability, and myelin degradation. Moreover, components of its activation cascade have been shown to present increased activity or expression in MS patients compared to controls; further studies are needed to clarify whether PLG is involved in MS susceptibility.
- Published
- 2016
50. Genome-wide association study in essential tremor identifies three new loci
- Author
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Müller, Stefanie H., primary, Girard, Simon L., additional, Hopfner, Franziska, additional, Merner, Nancy D., additional, Bourassa, Cynthia V., additional, Lorenz, Delia, additional, Clark, Lorraine N., additional, Tittmann, Lukas, additional, Soto-Ortolaza, Alexandra I., additional, Klebe, Stephan, additional, Hallett, Mark, additional, Schneider, Susanne A., additional, Hodgkinson, Colin A., additional, Lieb, Wolfgang, additional, Wszolek, Zbigniew K., additional, Pendziwiat, Manuela, additional, Lorenzo-Betancor, Oswaldo, additional, Poewe, Werner, additional, Ortega-Cubero, Sara, additional, Seppi, Klaus, additional, Rajput, Alex, additional, Hussl, Anna, additional, Rajput, Ali H., additional, Berg, Daniela, additional, Dion, Patrick A., additional, Wurster, Isabel, additional, Shulman, Joshua M., additional, Srulijes, Karin, additional, Haubenberger, Dietrich, additional, Pastor, Pau, additional, Vilariño-Güell, Carles, additional, Postuma, Ronald B., additional, Bernard, Geneviève, additional, Ladwig, Karl-Heinz, additional, Dupré, Nicolas, additional, Jankovic, Joseph, additional, Strauch, Konstantin, additional, Panisset, Michel, additional, Winkelmann, Juliane, additional, Testa, Claudia M., additional, Reischl, Eva, additional, Zeuner, Kirsten E., additional, Ross, Owen A., additional, Arzberger, Thomas, additional, Chouinard, Sylvain, additional, Deuschl, Günther, additional, Louis, Elan D., additional, Kuhlenbäumer, Gregor, additional, and Rouleau, Guy A., additional
- Published
- 2016
- Full Text
- View/download PDF
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