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1. The Parkinson’s disease risk gene cathepsin B promotes fibrillar alpha-synuclein clearance, lysosomal function and glucocerebrosidase activity in dopaminergic neurons

Author

Jones-Tabah, Jace, He, Kathy, Karpilovsky, Nathan, Senkevich, Konstantin, Deyab, Ghislaine, Pietrantonio, Isabella, Goiran, Thomas, Cousineau, Yuting, Nikanorova, Daria, Goldsmith, Taylor, del Cid Pellitero, Esther, Chen, Carol X.-Q., Luo, Wen, You, Zhipeng, Abdian, Narges, Ahmad, Jamil, Ruskey, Jennifer A., Asayesh, Farnaz, Spiegelman, Dan, Fahn, Stanley, Waters, Cheryl, Monchi, Oury, Dauvilliers, Yves, Dupré, Nicolas, Miliukhina, Irina, Timofeeva, Alla, Emelyanov, Anton, Pchelina, Sofya, Greenbaum, Lior, Hassin-Baer, Sharon, Alcalay, Roy N., Milnerwood, Austen, Durcan, Thomas M., Gan-Or, Ziv, and Fon, Edward A.

Published
2024
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2. Are rare heterozygous SYNJ1 variants associated with Parkinson’s disease?

Author

Senkevich, Konstantin, Parlar, Sitki Cem, Chantereault, Cloe, Yu, Eric, Ahmad, Jamil, Ruskey, Jennifer A., Asayesh, Farnaz, Spiegelman, Dan, Waters, Cheryl, Monchi, Oury, Dauvilliers, Yves, Dupré, Nicolas, Miliukhina, Irina, Timofeeva, Alla, Emelyanov, Anton, Pchelina, Sofya, Greenbaum, Lior, Hassin-Baer, Sharon, Alcalay, Roy N., and Gan-Or, Ziv

Published
2024
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3. Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects

Author

Krohn, Lynne, Heilbron, Karl, Blauwendraat, Cornelis, Reynolds, Regina H., Yu, Eric, Senkevich, Konstantin, Rudakou, Uladzislau, Estiar, Mehrdad A., Gustavsson, Emil K., Brolin, Kajsa, Ruskey, Jennifer A., Freeman, Kathryn, Asayesh, Farnaz, Chia, Ruth, Arnulf, Isabelle, Hu, Michele T. M., Montplaisir, Jacques Y., Gagnon, Jean-François, Desautels, Alex, Dauvilliers, Yves, Gigli, Gian Luigi, Valente, Mariarosaria, Janes, Francesco, Bernardini, Andrea, Högl, Birgit, Stefani, Ambra, Ibrahim, Abubaker, Šonka, Karel, Kemlink, David, Oertel, Wolfgang, Janzen, Annette, Plazzi, Giuseppe, Biscarini, Francesco, Antelmi, Elena, Figorilli, Michela, Puligheddu, Monica, Mollenhauer, Brit, Trenkwalder, Claudia, Sixel-Döring, Friederike, Cochen De Cock, Valérie, Monaca, Christelle Charley, Heidbreder, Anna, Ferini-Strambi, Luigi, Dijkstra, Femke, Viaene, Mineke, Abril, Beatriz, Boeve, Bradley F., Scholz, Sonja W., Ryten, Mina, Bandres-Ciga, Sara, Noyce, Alastair, Cannon, Paul, Pihlstrøm, Lasse, Nalls, Mike A., Singleton, Andrew B., Rouleau, Guy A., Postuma, Ronald B., and Gan-Or, Ziv

Published
2022
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4. Genome-wide association study of glucocerebrosidase activity modifiers.

Author

Somerville, Emma N., primary, Krohn, Lynne, additional, Senkevich, Konstanin, additional, Yu, Eric, additional, Ahmad, Jamil, additional, Asayesh, Farnaz, additional, Ruskey, Jennifer A., additional, Speigelman, Dan, additional, Fahn, Stanley, additional, Waters, Cheryl, additional, Sardi, S. Pablo, additional, Alcalay, Roy N., additional, and Gan-Or, Ziv, additional

Published
2024
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5. Autosomal Dominant Parkinson's Disease Caused by SNCA p.E46K Mutation in a Family with Russian Ancestry

Author

Senkevich, Konstantin, primary, Miliukhina, Irina, additional, Zhuravlev, Alexandr, additional, Shumilova, Maria, additional, Beletskaia, Mariia, additional, Skvortsova, Tatiana, additional, Yu, Eric, additional, Ahmad, Jamil, additional, Asayesh, Farnaz, additional, Gan‐Or, Ziv, additional, Emelyanov, Anton, additional, and Pchelina, Sofya, additional

Published
2024
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6. Genome-wide association study of glucocerebrosidase activity modifiers.

Author

Somerville, Emma N, primary, Krohn, Lynne, additional, Senkevich, Konstantin, additional, Yu, Eric, additional, Ahmad, Jamil, additional, Asayesh, Farnaz, additional, Ruskey, Jennifer A., additional, Spiegelman, Dan, additional, Fahn, Stanley, additional, Waters, Cheryl, additional, Sardi, S. Pablo, additional, Alcalay, Roy N., additional, and Gan-Or, Ziv, additional

Published
2024
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7. The Parkinson’s disease risk gene cathepsin B promotes fibrillar alpha-synuclein clearance, lysosomal function and glucocerebrosidase activity in dopaminergic neurons

Author

Jones-Tabah, Jace, primary, He, Kathy, additional, Senkevich, Konstantin, additional, Karpilovsky, Nathan, additional, Deyab, Ghislaine, additional, Cousineau, Yuting, additional, Nikanorova, Daria, additional, Goldsmith, Taylor, additional, Pellitero, Esther del-Cid, additional, Chen, Carol XQ, additional, Luo, Wen, additional, You, Zhipeng, additional, Abdian, Narges, additional, Pietrantonio, Isabella, additional, Goiran, Thomas, additional, Ahmad, Jamil, additional, Ruskey, Jennifer A, additional, Asayesh, Farnaz, additional, Spiegelman, Dan, additional, Waters, Cheryl, additional, Monchi, Oury, additional, Dauvilliers, Yves, additional, Dupre, Nicolas, additional, Miliukhina, Irina, additional, Timofeeva, Alla, additional, Emelyanov, Anton, additional, Pchelina, Sofya, additional, Greenbaum, Lior, additional, HassinBaer, Sharon, additional, Alcalay, Roy N, additional, Milnerwood, Austen, additional, Durcan, Thomas M, additional, Gan-Or, Ziv, additional, and Fon, Edward A, additional

Published
2024
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8. Fine mapping of the HLA locus in Parkinson’s disease in Europeans

Author

Yu, Eric, Ambati, Aditya, Andersen, Maren Stolp, Krohn, Lynne, Estiar, Mehrdad A., Saini, Prabhjyot, Senkevich, Konstantin, Sosero, Yuri L., Sreelatha, Ashwin Ashok Kumar, Ruskey, Jennifer A., Asayesh, Farnaz, Spiegelman, Dan, Toft, Mathias, Viken, Marte K., Sharma, Manu, Blauwendraat, Cornelis, Pihlstrøm, Lasse, Mignot, Emmanuel, and Gan-Or, Ziv

Published
2021
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9. The Parkinson's disease risk gene cathepsin B promotes fibrillar alpha-synuclein clearance, lysosomal function and glucocerebrosidase activity in dopaminergic neurons

Author

Jones-Tabah, Jace, primary, He, Kathy, additional, Senkevich, Konstantin, additional, Karpilovsky, Nathan, additional, Deyab, Ghislaine, additional, Cousineau, Yuting, additional, Nikanorova, Daria, additional, Goldsmith, Taylor, additional, del Cid Pellitero, Esther, additional, Chen, Carol X-Q, additional, Luo, Wen, additional, You, Zhipeng, additional, Abdian, Narges, additional, Pietrantonio, Isabella, additional, Goiran, Thomas, additional, Ahmad, Jamil, additional, Ruskey, Jennifer A, additional, Asayesh, Farnaz, additional, Spiegelman, Dan, additional, Fahn, Stanley, additional, Waters, Cheryl, additional, Monchi, Oury, additional, Dauvilliers, Yves, additional, Dupre, Nicolas, additional, Miliukhina, Irina, additional, Timofeeva, Alla, additional, Emelyanov, Anton, additional, Pchelina, Sofya, additional, Greenbaum, Lior, additional, Hassin-Baer, Sharon, additional, Alcalay, Roy N, additional, Milnerwood, Austen, additional, Durcan, Thomas M, additional, Gan-Or, Ziv, additional, and Fon, Edward A, additional

Published
2023
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10. Novel Associations of BST1 and LAMP3 with Rapid Eye Movement Sleep Behavior Disorder

Author

Mufti, Kheireddin, Yu, Eric, Rudakou, Uladzislau, Krohn, Lynne, Ruskey, Jennifer A., Asayesh, Farnaz, Laurent, Sandra B., Spiegelman, Dan, Arnulf, Isabelle, Hu, Michele T.M., Montplaisir, Jacques Y., Gagnon, Jean-François, Desautels, Alex, Dauvilliers, Yves, Gigli, Gian Luigi, Valente, Mariarosaria, Janes, Francesco, Bernardini, Andrea, Högl, Birgit, Stefani, Ambra, Holzknecht, Evi, Sonka, Karel, Kemlink, David, Oertel, Wolfgang, Janzen, Annette, Plazzi, Giuseppe, Antelmi, Elena, Figorilli, Michela, Puligheddu, Monica, Mollenhauer, Brit, Trenkwalder, Claudia, Sixel-Döring, Friederike, De Cock, Valérie Cochen, Monaca, Christelle Charley, Heidbreder, Anna, Ferini-Strambi, Luigi, Dijkstra, Femke, Viaene, Mineke, Abril, Beatriz, Boeve, Bradley F., Trempe, Jean-François, Rouleau, Guy A., Postuma, Ronald B., and Gan-Or, Ziv

Published
2021
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11. Dopamine pathway and Parkinson’s risk variants are associated with levodopa-induced dyskinesia

Author

Sosero, Yuri L., primary, Bandres-Ciga, Sara, additional, Ferwerda, Bart, additional, Tocino, Maria T. P., additional, Belloso, Dìaz R., additional, Gómez-Garre, Pilar, additional, Faouzi, Johann, additional, Taba, Pille, additional, Pavelka, Lukas, additional, Marques, Tainà M., additional, Gomes, Clarissa P. C., additional, Kolodkin, Alexey, additional, May, Patrick, additional, Milanowski, Lukasz M, additional, Wszolek, Zbigniew K., additional, Uitti, Ryan J., additional, Heutink, Peter, additional, van Hilten, Jacobus J., additional, Simon, David K., additional, Eberly, Shirley, additional, Alvarez, Ignacio, additional, Krohn, Lynne, additional, Yu, Eric, additional, Freeman, Kathryn, additional, Rudakou, Uladzislau, additional, Ruskey, Jennifer A., additional, Asayesh, Farnaz, additional, Menéndez-Gonzàlez, Manuel, additional, Pastor, Pau, additional, Ross, Owen A., additional, Krüger, Rejko, additional, Corvol, Jean-Christophe, additional, Koks, Sulev, additional, Mir, Pablo, additional, De Bie, Rob M.A., additional, Iwaki, Hirotaka, additional, and Gan-Or, Ziv, additional

Published
2023
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12. GBA variants in REM sleep behavior disorder: A multicenter study

Author

Krohn, Lynne, Ruskey, Jennifer A., Rudakou, Uladzislau, Leveille, Etienne, Asayesh, Farnaz, Hu, Michele T.M., Arnulf, Isabelle, Dauvilliers, Yves, Högl, Birgit, Stefani, Ambra, Monaca, Christelle Charley, Abril, Beatriz, Plazzi, Giuseppe, Antelmi, Elena, Ferini-Strambi, Luigi, Heidbreder, Anna, Boeve, Bradley F., Espay, Alberto J., De Cock, Valérie Cochen, Mollenhauer, Brit, Sixel-Döring, Friederike, Trenkwalder, Claudia, Sonka, Karel, Kemlink, David, Figorilli, Michela, Puligheddu, Monica, Dijkstra, Femke, Viaene, Mineke, Oertel, Wolfgang, Toffoli, Marco, Gigli, Gian Luigi, Valente, Mariarosaria, Gagnon, Jean-François, Desautels, Alex, Montplaisir, Jacques Y., Postuma, Ronald B., Rouleau, Guy A., and Gan-Or, Ziv

Published
2020
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15. Rare TMEM230 Variants are Potentially Associated With Early Onset Parkinson’s Disease (P3-11.013)

Author

Senkevich, Konstantin, primary, Yu, Eric, additional, Rudakou, Uladzislau, additional, Ahmad, Jamil, additional, Ruskey, Jennifer, additional, Asayesh, Farnaz, additional, Spiegelman, Dan, additional, Fahn, Stanley, additional, Waters, Cheryl, additional, Monchi, Oury, additional, Dauvilliers, Yves, additional, Dupre, Nicolas, additional, Miliukhina, Irina, additional, Timofeeva, Alla, additional, Kulabukhova, Daria, additional, Emelyanov, Anton, additional, Pchelina, Sofya, additional, Greenbaum, Lior, additional, Hassin, Sharon, additional, Alcalay, Roy, additional, and Gan-Or, Ziv, additional

Published
2023
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16. Association of Rare Variants in ARSA with Parkinson's Disease.

Author

Senkevich, Konstantin, Beletskaia, Mariia, Dworkind, Aliza, Yu, Eric, Ahmad, Jamil, Ruskey, Jennifer A., Asayesh, Farnaz, Spiegelman, Dan, Fahn, Stanley, Waters, Cheryl, Monchi, Oury, Dauvilliers, Yves, Dupré, Nicolas, Greenbaum, Lior, Hassin‐Baer, Sharon, Nagornov, Ilya, Tyurin, Alexandr, Miliukhina, Irina, Timofeeva, Alla, and Emelyanov, Anton

Abstract

Background: Several lysosomal genes are associated with Parkinson's disease (PD), yet the association between PD and ARSA remains unclear. Objectives: To study rare ARSA variants in PD. Methods: To study rare ARSA variants (minor allele frequency < 0.01) in PD, we performed burden analyses in six independent cohorts with 5801 PD patients and 20,475 controls, followed by a meta‐analysis. Results: We found evidence for associations between functional ARSA variants and PD in four cohorts (P ≤ 0.05 in each) and in the meta‐analysis (P = 0.042). We also found an association between loss‐of‐function variants and PD in the United Kingdom Biobank cohort (P = 0.005) and in the meta‐analysis (P = 0.049). These results should be interpreted with caution as no association survived multiple comparisons correction. Additionally, we describe two families with potential co‐segregation of ARSA p.E382K and PD. Conclusions: Rare functional and loss‐of‐function ARSA variants may be associated with PD. Further replications in large case–control/familial cohorts are required. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Published
2023
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17. Association of rare variants inARSAwith Parkinson’s disease

Author

Senkevich, Konstantin, primary, Beletskaia, Mariia, additional, Dworkind, Aliza, additional, Yu, Eric, additional, Ahmad, Jamil, additional, Ruskey, Jennifer A., additional, Asayesh, Farnaz, additional, Spiegelman, Dan, additional, Fahn, Stanley, additional, Waters, Cheryl, additional, Monchi, Oury, additional, Dauvilliers, Yves, additional, Dupré, Nicolas, additional, Greenbaum, Lior, additional, Hassin-Baer, Sharon, additional, Nagornov, Ilya, additional, Tyurin, Alexandr, additional, Miliukhina, Irina, additional, Timofeeva, Alla, additional, Emelyanov, Anton, additional, Zakharova, Ekaterina, additional, Alcalay, Roy N., additional, Pchelina, Sofya, additional, and Gan-Or, Ziv, additional

Published
2023
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18. NPC1 variants are not associated with Parkinson’s disease, REM-sleep behavior disorder or dementia with Lewy bodies in European cohorts

Author

Somerville, Emma N., primary, Krohn, Lynne, additional, Yu, Eric, additional, Rudakou, Uladzislau, additional, Senkevich, Konstantin, additional, Ruskey, Jennifer A., additional, Asayesh, Farnaz, additional, Ahmad, Jamil, additional, Spiegelman, Dan, additional, Dauvilliers, Yves, additional, Arnulf, Isabelle, additional, Hu, Michele T.M., additional, Montplaisir, Jacques Y., additional, Gagnon, Jean-François, additional, Desautels, Alex, additional, Ibrahim, Abubaker, additional, Stefani, Ambra, additional, Högl, Birgit, additional, Gigli, Gian Luigi, additional, Valente, Mariarosaria, additional, Janes, Francesco, additional, Bernardini, Andrea, additional, Dusek, Petr, additional, Sonka, Karel, additional, Kemlink, David, additional, Plazzi, Giuseppe, additional, Antelmi, Elena, additional, Biscarini, Francesco, additional, Mollenhauer, Brit, additional, Trenkwalder, Claudia, additional, Sixel-Doring, Friederike, additional, Figorilli, Michela, additional, Puligheddu, Monica, additional, De Cock, Valerie Cochen, additional, Oertel, Wolfgang, additional, Janzen, Annette, additional, Ferini-Strambi, Luigi, additional, Heibreder, Anna, additional, Monaca, Christelle Charley, additional, Abril, Beatriz, additional, Dijkstra, Femke, additional, Viaene, Mineke, additional, Boeve, Bradley F., additional, Postuma, Ronald B., additional, Rouleau, Guy A., additional, and Gan-Or, Ziv, additional

Published
2023
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20. GALC variants affect galactosylceramidase enzymatic activity and risk of Parkinson’s disease

Author

Senkevich, Konstantin, primary, Zorca, Cornelia E, additional, Dworkind, Aliza, additional, Rudakou, Uladzislau, additional, Somerville, Emma, additional, Yu, Eric, additional, Ermolaev, Alexey, additional, Nikanorova, Daria, additional, Ahmad, Jamil, additional, Ruskey, Jennifer A, additional, Asayesh, Farnaz, additional, Spiegelman, Dan, additional, Fahn, Stanley, additional, Waters, Cheryl, additional, Monchi, Oury, additional, Dauvilliers, Yves, additional, Dupré, Nicolas, additional, Greenbaum, Lior, additional, Hassin-Baer, Sharon, additional, Grenn, Francis P, additional, Chiang, Ming Sum Ruby, additional, Sardi, S Pablo, additional, Vanderperre, Benoît, additional, Blauwendraat, Cornelis, additional, Trempe, Jean-François, additional, Fon, Edward A, additional, Durcan, Thomas M, additional, Alcalay, Roy N, additional, and Gan-Or, Ziv, additional

Published
2022
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21. NPC1variants are not associated with Parkinson’s Disease, REM-sleep behaviour disorder or Dementia with Lewy bodies in European cohorts

Author

Somerville, Emma N., primary, Krohn, Lynne, additional, Yu, Eric, additional, Rudakou, Uladzislau, additional, Senkevich, Konstantin, additional, Ruskey, Jennifer A., additional, Asayesh, Farnaz, additional, Ahmad, Jamil, additional, Spiegelman, Dan, additional, Dauvilliers, Yves, additional, Arnulf, Isabelle, additional, Hu, Michele T.M., additional, Montplaisir, Jacques Y., additional, Gagnon, Jean-François, additional, Desautels, Alex, additional, Ibrahim, Abubaker, additional, Stefani, Ambra, additional, Hogl, Birgit, additional, Gigli, Gian Luigi, additional, Valente, Mariarosaria, additional, Janes, Francesco, additional, Bernardini, Andrea, additional, Dusek, Petr, additional, Sonka, Karel, additional, Kemlink, David, additional, Plazzi, Giuseppe, additional, Antelmi, Elena, additional, Biscarini, Francesco, additional, Mollenhauer, Brit, additional, Trenkwalder, Claudia, additional, Sixel-Doring, Friederike, additional, Figorilli, Michela, additional, Puligheddu, Monica, additional, De Cock, Valerie Cochen, additional, Ferini-Strambi, Luigi, additional, Heibreder, Anna, additional, Monaca, Christelle Charley, additional, Abril, Beatriz, additional, Dijkstra, Femke, additional, Viaene, Mineke, additional, Boeve, Bradley F., additional, Postuma, Ronald B., additional, Rouleau, Guy A., additional, and Gan-Or, Ziv, additional

Published
2022
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22. Gene-based burden analysis of damaging private variants in PRKN, PARK7 and PINK1 in Parkinson's disease cohorts of European descent

Author

Hu, Jing, primary, Waters, Cheryl H., additional, Spiegelman, Dan, additional, Fon, Edward A., additional, Yu, Eric, additional, Asayesh, Farnaz, additional, Krohn, Lynne, additional, Saini, Prabhjyot, additional, Alcalay, Roy N., additional, Hassin-Baer, Sharon, additional, Gan-Or, Ziv, additional, Krainc, Dimitri, additional, Zhang, BaoRong, additional, Bustos, Bernabe I., additional, and Lubbe, Steven J., additional

Published
2022
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23. HLA in isolated REM sleep behavior disorder and Lewy body dementia.

Author

Yu, Eric, Krohn, Lynne, Ruskey, Jennifer A., Asayesh, Farnaz, Spiegelman, Dan, Shah, Zalak, Chia, Ruth, Arnulf, Isabelle, Hu, Michele T. M., Montplaisir, Jacques Y., Gagnon, Jean‐François, Desautels, Alex, Dauvilliers, Yves, Gigli, Gian Luigi, Valente, Mariarosaria, Janes, Francesco, Bernardini, Andrea, Högl, Birgit, Stefani, Ambra, and Ibrahim, Abubaker

Subjects
LEWY body dementia, RAPID eye movement sleep, SLEEP disorders, HLA histocompatibility antigens
Abstract

Synucleinopathies‐related disorders such as Lewy body dementia (LBD) and isolated/idiopathic REM sleep behavior disorder (iRBD) have been associated with neuroinflammation. In this study, we examined whether the human leukocyte antigen (HLA) locus plays a role in iRBD and LBD. In iRBD, HLA‐DRB1*11:01 was the only allele passing FDR correction (OR = 1.57, 95% CI = 1.27–1.93, p = 2.70e‐05). We also discovered associations between iRBD and HLA‐DRB1 70D (OR = 1.26, 95%CI = 1.12–1.41, p = 8.76e‐05), 70Q (OR = 0.81, 95%CI = 0.72–0.91, p = 3.65e‐04) and 71R (OR = 1.21, 95%CI = 1.08–1.35, p = 1.35e‐03). Position 71 (pomnibus = 0.00102) and 70 (pomnibus = 0.00125) were associated with iRBD. Our results suggest that the HLA locus may have different roles across synucleinopathies. [ABSTRACT FROM AUTHOR]

Published
2023
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24. GALC variants affect galactosylceramidase enzymatic activity and risk of Parkinson's disease.

Author

Senkevich, Konstantin, Zorca, Cornelia E, Dworkind, Aliza, Rudakou, Uladzislau, Somerville, Emma, Yu, Eric, Ermolaev, Alexey, Nikanorova, Daria, Ahmad, Jamil, Ruskey, Jennifer A, Asayesh, Farnaz, Spiegelman, Dan, Fahn, Stanley, Waters, Cheryl, Monchi, Oury, Dauvilliers, Yves, Dupré, Nicolas, Greenbaum, Lior, Hassin-Baer, Sharon, and Grenn, Francis P

Subjects
PARKINSON'S disease, GENOME-wide association studies, GENE expression, CRISPRS, CHROMOSOMES
Abstract

The association between glucocerebrosidase (GCase), encoded by GBA, and Parkinson's disease highlights the role of the lysosome in Parkinson's disease pathogenesis. Genome-wide association studies (GWAS) in Parkinson's disease have revealed multiple associated loci, including the GALC locus on chromosome 14. GALC encodes the lysosomal enzyme galactosylceramidase (GalCase), which plays a pivotal role in the glycosphingolipid metabolism pathway. It is still unclear whether GALC is the gene driving the association in the chromosome 14 locus, and if so, by which mechanism. We first aimed to examine whether variants in the GALC locus and across the genome are associated with GalCase activity. We performed a GWAS in two independent cohorts from a)Columbia University and b)the Parkinson's Progression Markers Initiative study, followed by a meta-analysis with a total of 976 Parkinson's disease patients and 478 controls with available data on GalCase activity. We further analyzed the effects of common GALC variants on expression and GalCase activity using genomic colocalization methods. Mendelian randomization was used to study whether GalCase activity may be causal in Parkinson's disease. To study the role of rare GALC variants we analyzed sequencing data from 5,028 Parkinson's disease patients and 5,422 controls. Additionally, we studied the functional impact of GALC knock-out on alpha-synuclein accumulation and on GCase activity in neuronal cell models and performed in silico structural analysis of common GALC variants associated with altered GalCase activity. The top hit in Parkinson's disease GWAS in the GALC locus, rs979812, is associated with increased GalCase activity (b = 1.2; se = 0.06; p = 5.10E-95). No other variants outside the GALC locus were associated with GalCase activity. Colocalization analysis demonstrated that rs979812 was also associated with increased GalCase expression. Mendelian randomization suggested that increased GalCase activity may be causally associated with Parkinson's disease (b = 0.025, se = 0.007, p = 0.0008). We did not find an association between rare GALC variants and Parkinson's disease. GALC knockout using CRISPR-Cas9 did not lead to alpha-synuclein accumulation, further supporting that increased rather than reduced GalCase levels may be associated with Parkinson's disease. The structural analysis demonstrated that the common variant p.I562T may lead to improper maturation of GalCase affecting its activity. Our results nominate GALC as the gene associated with Parkinson's disease in this locus and suggest that the association of variants in the GALC locus may be driven by their effect of increasing GalCase expression and activity. Whether altering GalCase activity could be considered as a therapeutic target should be further studied. [ABSTRACT FROM AUTHOR]

Published
2023
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25. GALCvariants affect galactosylceramidase enzymatic activity and risk of Parkinson’s disease

Author

Senkevich, Konstantin, primary, Zorca, Cornelia E., additional, Dworkind, Aliza, additional, Rudakou, Uladzislau, additional, Somerville, Emma, additional, Yu, Eric, additional, Ermolaev, Alexey, additional, Nikanorova, Daria, additional, Ahmad, Jamil, additional, Ruskey, Jennifer A., additional, Asayesh, Farnaz, additional, Spiegelman, Dan, additional, Fahn, Stanley, additional, Waters, Cheryl, additional, Monchi, Oury, additional, Dauvilliers, Yves, additional, Dupré, Nicolas, additional, Greenbaum, Lior, additional, Hassin-Baer, Sharon, additional, Grenn, Francis P., additional, Ruby Chiang, Ming Sum, additional, Sardi, S. Pablo, additional, Vanderperre, Benoît, additional, Blauwendraat, Cornelis, additional, Trempe, Jean-François, additional, Fon, Edward A., additional, Durcan, Thomas M., additional, Alcalay, Roy N., additional, and Gan-Or, Ziv, additional

Published
2022
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26. Rare PSAP Variants and Possible Interaction with GBA in REM Sleep Behavior Disorder

Author

Sosero, Yuri L., primary, Yu, Eric, additional, Estiar, Mehrdad A., additional, Krohn, Lynne, additional, Mufti, Kheireddin, additional, Rudakou, Uladzislau, additional, Ruskey, Jennifer A., additional, Asayesh, Farnaz, additional, Laurent, Sandra B., additional, Spiegelman, Dan, additional, Trempe, Jean-François, additional, Quinnell, Timothy G., additional, Oscroft, Nicholas, additional, Arnulf, Isabelle, additional, Montplaisir, Jacques Y., additional, Gagnon, Jean-François, additional, Desautels, Alex, additional, Dauvilliers, Yves, additional, Gigli, Gian Luigi, additional, Valente, Mariarosaria, additional, Janes, Francesco, additional, Bernardini, Andrea, additional, Sonka, Karel, additional, Kemlink, David, additional, Oertel, Wolfgang, additional, Janzen, Annette, additional, Plazzi, Giuseppe, additional, Antelmi, Elena, additional, Biscarini, Francesco, additional, Figorilli, Michela, additional, Puligheddu, Monica, additional, Mollenhauer, Brit, additional, Trenkwalder, Claudia, additional, Sixel-Döring, Friederike, additional, Cochen De Cock, Valérie, additional, Monaca, Christelle Charley, additional, Heidbreder, Anna, additional, Ferini-Strambi, Luigi, additional, Dijkstra, Femke, additional, Viaene, Mineke, additional, Abril, Beatriz, additional, Boeve, Bradley F., additional, Postuma, Ronald B., additional, Rouleau, Guy A., additional, Ibrahim, Abubaker, additional, Stefani, Ambra, additional, Högl, Birgit, additional, Hu, Michele T.M., additional, and Gan-Or, Ziv, additional

Published
2022
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27. Rare PSAP variants and possible interaction with GBA in REM sleep behavior disorder

Author

Sosero, Yuri L., primary, Yu, Eric, additional, Estiar, Mehrdad A., additional, Krohn, Lynne, additional, Mufti, Kheireddin, additional, Rudakou, Uladzislau, additional, Ruskey, Jennifer A., additional, Asayesh, Farnaz, additional, Laurent, Sandra B., additional, Spiegelman, Dan, additional, Trempe, Jean-François, additional, Quinnell, Timothy G., additional, Oscroft, Nicholas, additional, Arnulf, Isabelle, additional, Montplaisir, Jacques Y., additional, Gagnon, Jean-François, additional, Desautels, Alex, additional, Dauvilliers, Yves, additional, Gigli, Gian Luigi, additional, Valente, Mariarosaria, additional, Janes, Francesco, additional, Bernardini, Andrea, additional, Sonka, Karel, additional, Kemlink, David, additional, Oertel, Wolfgang, additional, Janzen, Annette, additional, Plazzi, Giuseppe, additional, Antelmi, Elena, additional, Biscarini, Francesco, additional, Figorilli, Michela, additional, Puligheddu, Monica, additional, Mollenhauer, Brit, additional, Trenkwalder, Claudia, additional, Sixel-Döring, Friederike, additional, De Cock, Valérie Cochen, additional, Monaca, Christelle Charley, additional, Heidbreder, Anna, additional, Ferini-Strambi, Luigi, additional, Dijkstra, Femke, additional, Viaene, Mineke, additional, Abril, Beatriz, additional, Boeve, Bradley F., additional, Postuma, Ronald B., additional, Rouleau, Guy A., additional, Ibrahim, Abubaker, additional, Stefani, Ambra, additional, Högl, Birgit, additional, Hu, Michele T.M., additional, and Gan-Or, Ziv, additional

Published
2021
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28. Microfluidic flow confinement to avoid chemotaxis-based upstream growth in a biofilm flow cell reactor

Author

Greener, Jesse, Zarabadi, Mirpouyan, Asayesh, Farnaz, Babaei Aznaveh, Nahid, Greener, Jesse, Zarabadi, Mirpouyan, Asayesh, Farnaz, and Babaei Aznaveh, Nahid

Abstract

Introduction of a bacterial inoculant into a chemostat bioreactor can lead to unwanted contamination of upstream elements via chemotaxis. This can result in biofilm growth in connective tubing, valves and even the medium source reservoir itself, thus complicating the conditions of the applied liquid phase and impeding proper chemostat functionality. Applied to biofilm forming Pseudomonas fluorescens bacteria, we tested two different microfluidic flow confinement methods designed to impede upstream contamination. The first isolated biofilm growth from the relatively stagnant zones within the microchannel corners, and in the second a flow enhancement element was introduced to increase flow velocities and shear forces. Both methods showed improvement over a control design, but flow enhancement showed the best performance by delaying or preventing bacterial contamination of upstream elements, ensuring stability of the applied liquid media conditions for the entire duration of the experiments. This simple passive element has the potential for wide use as it is easy to implement and can be optimised for different experimental requirements.

Published
2020

29. Novel Associations of BST1 and LAMP3 With REM Sleep Behavior Disorder

Author

Mufti, Kheireddin, primary, Yu, Eric, additional, Rudakou, Uladzislau, additional, Krohn, Lynne, additional, Ruskey, Jennifer A., additional, Asayesh, Farnaz, additional, Laurent, Sandra B., additional, Spiegelman, Dan, additional, Arnulf, Isabelle, additional, Hu, Michele T.M., additional, Montplaisir, Jacques Y., additional, Gagnon, Jean-François, additional, Desautels, Alex, additional, Dauvilliers, Yves, additional, Gigli, Gian Luigi, additional, Valente, Mariarosaria, additional, Janes, Francesco, additional, Bernardini, Andrea, additional, Högl, Birgit, additional, Stefani, Ambra, additional, Holzknecht, Evi, additional, Sonka, Karel, additional, Kemlink, David, additional, Oertel, Wolfgang, additional, Janzen, Annette, additional, Plazzi, Giuseppe, additional, Antelmi, Elena, additional, Figorilli, Michela, additional, Puligheddu, Monica, additional, Mollenhauer, Brit, additional, Trenkwalder, Claudia, additional, Sixel-Döring, Friederike, additional, Cochen De Cock, Valérie, additional, Monaca, Christelle Charley, additional, Heidbreder, Anna, additional, Ferini-Strambi, Luigi, additional, Dijkstra, Femke, additional, Viaene, Mineke, additional, Abril, Beatriz, additional, Boeve, Bradley F., additional, Trempe, Jean-François, additional, Rouleau, Guy A., additional, Postuma, Ronald B., additional, and Gan-Or, Ziv, additional

Published
2021
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30. Evidence for Non‐Mendelian Inheritance in Spastic Paraplegia 7

Author

Estiar, Mehrdad A., primary, Yu, Eric, additional, Haj Salem, Ikhlass, additional, Ross, Jay P., additional, Mufti, Kheireddin, additional, Akçimen, Fulya, additional, Leveille, Etienne, additional, Spiegelman, Dan, additional, Ruskey, Jennifer A., additional, Asayesh, Farnaz, additional, Dagher, Alain, additional, Yoon, Grace, additional, Tarnopolsky, Mark, additional, Boycott, Kym M., additional, Dupre, Nicolas, additional, Dion, Patrick A., additional, Suchowersky, Oksana, additional, Trempe, Jean‐Francois, additional, Rouleau, Guy A., additional, and Gan‐Or, Ziv, additional

Published
2021
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31. Targeted sequencing of Parkinson’s disease loci genes highlights SYT11, FGF20 and other associations

Author

Rudakou, Uladzislau, primary, Yu, Eric, additional, Krohn, Lynne, additional, Ruskey, Jennifer A, additional, Asayesh, Farnaz, additional, Dauvilliers, Yves, additional, Spiegelman, Dan, additional, Greenbaum, Lior, additional, Fahn, Stanley, additional, Waters, Cheryl H, additional, Dupré, Nicolas, additional, Rouleau, Guy A, additional, Hassin-Baer, Sharon, additional, Fon, Edward A, additional, Alcalay, Roy N, additional, and Gan-Or, Ziv, additional

Published
2020
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32. Fine mapping of the HLA locus in Parkinson’s disease in Europeans

Author

Yu, Eric, primary, Ambati, Aditya, additional, Andersen, Maren Stolp, additional, Krohn, Lynne, additional, Estiar, Mehrdad A., additional, Saini, Prabhjyot, additional, Senkevich, Konstantin, additional, Sosero, Yuri L., additional, Kumar Sreelatha, Ashwin Ashok, additional, Ruskey, Jennifer A., additional, Asayesh, Farnaz, additional, Spiegelman, Dan, additional, Toft, Mathias, additional, Viken, Marte K., additional, Sharma, Manu, additional, Blauwendraat, Cornelis, additional, Pihlstrøm, Lasse, additional, Mignot, Emmanuel, additional, and Gan-Or, Ziv, additional

Published
2020
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33. Comprehensive Analysis of Familial Parkinsonism Genes in Rapid‐Eye‐Movement Sleep Behavior Disorder

Author

Mufti, Kheireddin, primary, Rudakou, Uladzislau, additional, Yu, Eric, additional, Krohn, Lynne, additional, Ruskey, Jennifer A., additional, Asayesh, Farnaz, additional, Laurent, Sandra B., additional, Spiegelman, Dan, additional, Arnulf, Isabelle, additional, Hu, Michele T.M., additional, Montplaisir, Jacques Y., additional, Gagnon, Jean‐François, additional, Desautels, Alex, additional, Dauvilliers, Yves, additional, Gigli, Gian Luigi, additional, Valente, Mariarosaria, additional, Janes, Francesco, additional, Högl, Birgit, additional, Stefani, Ambra, additional, Holzknecht, Evi, additional, Šonka, Karel, additional, Kemlink, David, additional, Oertel, Wolfgang, additional, Janzen, Annette, additional, Plazzi, Giuseppe, additional, Antelmi, Elena, additional, Figorilli, Michela, additional, Puligheddu, Monica, additional, Mollenhauer, Brit, additional, Trenkwalder, Claudia, additional, Sixel‐Döring, Friederike, additional, Cochen De Cock, Valérie, additional, Monaca, Christelle Charley, additional, Heidbreder, Anna, additional, Ferini‐Strambi, Luigi, additional, Dijkstra, Femke, additional, Viaene, Mineke, additional, Abril, Beatriz, additional, Boeve, Bradley F., additional, Postuma, Ronald B., additional, Rouleau, Guy A., additional, and Gan‐Or, Ziv, additional

Published
2020
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34. Evidence for non-Mendelian inheritance in spastic paraplegia 7

Author

Estiar, Mehrdad A, primary, Yu, Eric, additional, Salem, Ikhlass Haj, additional, Ross, Jay P., additional, Mufti, Kheireddin, additional, Akçimen, Fulya, additional, Leveille, Etienne, additional, Spiegelman, Dan, additional, Ruskey, Jennifer A., additional, Asayesh, Farnaz, additional, Dagher, Alain, additional, Yoon, Grace, additional, Tarnopolsky, Mark, additional, Boycott, Kym M., additional, Dupre, Nicolas, additional, Dion, Patrick A., additional, Suchowersky, Oksana, additional, Trempe, Jean-Francois, additional, Rouleau, Guy A., additional, and Gan-Or, Ziv, additional

Published
2020
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35. Analysis of Heterozygous PRKN Variants and Copy‐Number Variations in Parkinson's Disease

Author

Yu, Eric, primary, Rudakou, Uladzislau, additional, Krohn, Lynne, additional, Mufti, Kheireddin, additional, Ruskey, Jennifer A., additional, Asayesh, Farnaz, additional, Estiar, Mehrdad A., additional, Spiegelman, Dan, additional, Surface, Matthew, additional, Fahn, Stanley, additional, Waters, Cheryl H., additional, Greenbaum, Lior, additional, Espay, Alberto J., additional, Dauvilliers, Yves, additional, Dupré, Nicolas, additional, Rouleau, Guy A., additional, Hassin‐Baer, Sharon, additional, Fon, Edward A., additional, Alcalay, Roy N., additional, and Gan‐Or, Ziv, additional

Published
2020
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36. Variants in the Niemann–Pick type C gene NPC1 are not associated with Parkinson's disease

Author

Ouled Amar Bencheikh, Bouchra, primary, Senkevich, Konstantin, additional, Rudakou, Uladzislau, additional, Yu, Eric, additional, Mufti, Kheireddin, additional, Ruskey, Jennifer A., additional, Asayesh, Farnaz, additional, Laurent, Sandra B., additional, Spiegelman, Dan, additional, Fahn, Stanley, additional, Waters, Cheryl, additional, Monchi, Oury, additional, Dauvilliers, Yves, additional, Espay, Alberto J., additional, Dupré, Nicolas, additional, Greenbaum, Lior, additional, Hassin-Baer, Sharon, additional, Rouleau, Guy A., additional, Alcalay, Roy N., additional, Fon, Edward A., additional, and Gan-Or, Ziv, additional

Published
2020
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37. Association study of DNAJC13, UCHL1, HTRA2, GIGYF2 and EIF4G1 with Parkinson’s disease

Author

Saini, Prabhjyot, primary, Rudakou, Uladzislau, additional, Yu, Eric, additional, Ruskey, Jennifer A., additional, Asayesh, Farnaz, additional, Laurent, Sandra B., additional, Spiegelman, Dan, additional, Fahn, Stanley, additional, Waters, Cheryl, additional, Monchi, Oury, additional, Dauvilliers, Yves, additional, Dupré, Nicolas, additional, Greenbaum, Lior, additional, Hassin-Baer, Sharon, additional, Espay, Alberto J., additional, Rouleau, Guy A., additional, Alcalay, Roy N., additional, Fon, Edward A., additional, Postuma, Ronald B., additional, and Gan-Or, Ziv, additional

Published
2020
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38. Novel associations of BST1 and LAMP3 with rapid eye movement sleep behavior disorder

Author

Mufti, Kheireddin, primary, Yu, Eric, additional, Rudakou, Uladzislau, additional, Krohn, Lynne, additional, Ruskey, Jennifer A., additional, Asayesh, Farnaz, additional, Laurent, Sandra B., additional, Spiegelman, Dan, additional, Arnulf, Isabelle, additional, Hu, Michele T.M., additional, Montplaisir, Jacques Y., additional, Gagnon, Jean-François, additional, Desautels, Alex, additional, Dauvilliers, Yves, additional, Gigli, Gian Luigi, additional, Valente, Mariarosaria, additional, Janes, Francesco, additional, Bernardini, Andrea, additional, Högl, Birgit, additional, Stefani, Ambra, additional, Holzknecht, Evi, additional, Sonka, Karel, additional, Kemlink, David, additional, Oertel, Wolfgang, additional, Janzen, Annette, additional, Plazzi, Giuseppe, additional, Antelmi, Elena, additional, Figorilli, Michela, additional, Puligheddu, Monica, additional, Mollenhauer, Brit, additional, Trenkwalder, Claudia, additional, Sixel-Döring, Friederike, additional, De Cock, Valérie Cochen, additional, Monaca, Christelle Charley, additional, Heidbreder, Anna, additional, Ferini-Strambi, Luigi, additional, Dijkstra, Femke, additional, Viaene, Mineke, additional, Abril, Beatriz, additional, Boeve, Bradley F., additional, Trempe, Jean-François, additional, Rouleau, Guy A., additional, Postuma, Ronald B., additional, and Gan-Or, Ziv, additional

Published
2020
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39. Targeted sequencing of Parkinson’s disease loci genes highlightsSYT11, FGF20and other associations

Author

Rudakou, Uladzislau, primary, Yu, Eric, additional, Krohn, Lynne, additional, Ruskey, Jennifer A., additional, Asayesh, Farnaz, additional, Dauvilliers, Yves, additional, Spiegelman, Dan, additional, Greenbaum, Lior, additional, Fahn, Stanley, additional, Waters, Cheryl H., additional, Dupré, Nicolas, additional, Rouleau, Guy A., additional, Hassin-Baer, Sharon, additional, Fon, Edward A., additional, Alcalay, Roy N., additional, and Gan-Or, Ziv, additional

Published
2020
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40. A comprehensive analysis of dominant and recessive parkinsonism genes in REM sleep behavior disorder

Author

Mufti, Kheireddin, primary, Rudakou, Uladzislau, additional, Yu, Eric, additional, Ruskey, Jennifer A., additional, Asayesh, Farnaz, additional, Laurent, Sandra B., additional, Spiegelman, Dan, additional, Arnulf, Isabelle, additional, Hu, Michele T.M., additional, Montplaisir, Jacques Y., additional, Gagnon, Jean-François, additional, Desautels, Alex, additional, Dauvilliers, Yves, additional, Gigli, Gian Luigi, additional, Valente, Mariarosaria, additional, Janes, Francesco, additional, Högl, Birgit, additional, Stefani, Ambra, additional, Holzknecht, Evi, additional, Sonka, Karel, additional, Kemlink, David, additional, Oertel, Wolfgang, additional, Janzen, Annette, additional, Plazzi, Giuseppe, additional, Antelmi, Elena, additional, Figorilli, Michela, additional, Puligheddu, Monica, additional, Mollenhauer, Brit, additional, Trenkwalder, Claudia, additional, Sixel-Döring, Friederike, additional, De Cock, Valérie Cochen, additional, Monaca, Christelle Charley, additional, Heidbreder, Anna, additional, Ferini-Strambi, Luigi, additional, Dijkstra, Femke, additional, Viaene, Mineke, additional, Abril, Beatriz, additional, Boeve, Bradley F., additional, Postuma, Ronald B., additional, Rouleau, Guy A., additional, and Gan-Or, Ziv, additional

Published
2020
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41. Variants in the Niemann-Pick type C gene NPC1 are not associated with Parkinson’s disease

Author

Amar Bencheikh, Bouchra Ouled, primary, Senkevich, Konstantin, additional, Rudakou, Uladzislau, additional, Yu, Eric, additional, Mufti, Kheireddin, additional, Ruskey, Jennifer A., additional, Asayesh, Farnaz, additional, Laurent, Sandra B., additional, Spiegelman, Dan, additional, Fahn, Stanley, additional, Waters, Cheryl, additional, Monchi, Oury, additional, Dauvilliers, Yves, additional, Espay, Alberto J., additional, Dupré, Nicolas, additional, Greenbaum, Lior, additional, Hassin-Baer, Sharon, additional, Rouleau, Guy A., additional, Alcalay, Roy N., additional, Fon, Edward A., additional, and Gan-Or, Ziv, additional

Published
2020
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42. Rare PSAPVariants and Possible Interaction with GBAin REM Sleep Behavior Disorder

Author

Sosero, Yuri L., Yu, Eric, Estiar, Mehrdad A., Krohn, Lynne, Mufti, Kheireddin, Rudakou, Uladzislau, Ruskey, Jennifer A., Asayesh, Farnaz, Laurent, Sandra B., Spiegelman, Dan, Trempe, Jean-François, Quinnell, Timothy G., Oscroft, Nicholas, Arnulf, Isabelle, Montplaisir, Jacques Y., Gagnon, Jean-François, Desautels, Alex, Dauvilliers, Yves, Gigli, Gian Luigi, Valente, Mariarosaria, Janes, Francesco, Bernardini, Andrea, Sonka, Karel, Kemlink, David, Oertel, Wolfgang, Janzen, Annette, Plazzi, Giuseppe, Antelmi, Elena, Biscarini, Francesco, Figorilli, Michela, Puligheddu, Monica, Mollenhauer, Brit, Trenkwalder, Claudia, Sixel-Döring, Friederike, Cochen De Cock, Valérie, Monaca, Christelle Charley, Heidbreder, Anna, Ferini-Strambi, Luigi, Dijkstra, Femke, Viaene, Mineke, Abril, Beatriz, Boeve, Bradley F., Postuma, Ronald B., Rouleau, Guy A., Ibrahim, Abubaker, Stefani, Ambra, Högl, Birgit, Hu, Michele T.M., and Gan-Or, Ziv

Abstract

PSAPencodes saposin C, the co-activator of glucocerebrosidase, encoded by GBA. GBAmutations are associated with idiopathic/isolated REM sleep behavior disorder (iRBD), a prodromal stage of synucleinopathy. To examine the role of PSAPmutations in iRBD. We fully sequenced PSAPand performed Optimized Sequence Kernel Association Test in 1,113 iRBD patients and 2,324 controls. We identified loss-of-function (LoF) mutations, which are very rare in PSAP, in three iRBD patients and none in controls (uncorrected p = 0.018). Two variants were stop mutations, p.Gln260Ter and p.Glu166Ter, and one was an in-frame deletion, p.332_333del. All three mutations have a deleterious effect on saposin C, based on in silicoanalysis. In addition, the two carriers of p.Glu166Ter and p.332_333del mutations also carried a GBAvariant, p.Arg349Ter and p.Glu326Lys, respectively. The co-occurrence of these extremely rare PSAPLoF mutations in two (0.2%) GBAvariant carriers in the iRBD cohort, is unlikely to occur by chance (estimated co-occurrence in the general population based on gnomAD data is 0.00035%). Although none of the three iRBD patients with PSAPLoF mutations have phenoconverted to an overt synucleinopathy at their last follow-up, all manifested initial signs suggestive of motor dysfunction, two were diagnosed with mild cognitive impairment and all showed prodromal clinical markers other than RBD. Their probability of prodromal PD, according to the Movement Disorder Society research criteria, was 98% or more. These results suggest a possible role of PSAPvariants in iRBD and potential genetic interaction with GBA, which requires additional studies.

Published
2022
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43. Shear stress effects on epididymal epithelial cell via primary cilia mechanosensory signaling.

Author

Fakhari, Sepideh, Campolina‐Silva, Gabriel, Asayesh, Farnaz, Girardet, Laura, Scott‐Boyer, Marie‐Pier, Droit, Arnaud, Soulet, Denis, Greener, Jesse, and Belleannée, Clémence

Subjects
*MALE reproductive organs, *SHEARING force, *CELL physiology, *FLUID flow, *EPITHELIAL cells
Abstract

Shear stress, resulting from fluid flow, is a fundamental mechanical stimulus affecting various cellular functions. The epididymis, essential for sperm maturation, offers a compelling model to study the effects of shear stress on cellular behavior. This organ undergoes extensive proliferation and differentiation until puberty, achieving full functionality as spermatozoa commence their post‐testicular maturation. Although the mechanical tension exerted by testicular fluid is hypothesized to drive epithelial proliferation and differentiation, the precise mechanisms remain unclear. Here we assessed whether the responsiveness of the epididymal cells to shear stress depends on functional primary cilia by combining microfluidic strategies on immortalized epididymal cells, calcium signaling assays, and high‐throughput gene expression analysis. We identified 97 genes overexpressed in response to shear stress, including early growth response (Egr) 2/3, cellular communication network factor (Ccn) 1/2, and Fos proto‐oncogene (Fos). While shear stress triggered a rapid increase of intracellular Ca2+, this response was abrogated following the impairment of primary ciliogenesis through pharmacological and siRNA approaches. Overall, our findings provide valuable insights into how mechanical forces influence the development of the male reproductive system, a requisite to sperm maturation. [ABSTRACT FROM AUTHOR]

Published
2024
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44. GBA variants in REM sleep behavior disorder: a multicenter study

Author

Krohn, Lynne, primary, Ruskey, Jennifer A., additional, Rudakou, Uladzislau, additional, Leveille, Etienne, additional, Asayesh, Farnaz, additional, Hu, Michele T.M., additional, Arnulf, Isabelle, additional, Dauvilliers, Yves, additional, Högl, Birgit, additional, Stefani, Ambra, additional, Monaca, Christelle Charley, additional, Beatriz, Abril, additional, Plazzi, Giuseppe, additional, Antelmi, Elena, additional, Ferini-Strambi, Luigi, additional, Heidbreder, Anna, additional, Boeve, Bradley F., additional, Espay, Alberto J., additional, De Cock, Valérie Cochen, additional, Mollenhauer, Brit, additional, Sixel-Döring, Friederike, additional, Trenkwalder, Claudia, additional, Sonka, Karel, additional, Kemlink, David, additional, Figorilli, Michela, additional, Puligheddu, Monica, additional, Dijkstra, Femke, additional, Viaene, Mineke, additional, Oertel, Wolfgang, additional, Toffoli, Marco, additional, Gigli, Gian Luigi, additional, Valente, Mariarosaria, additional, Gagnon, Jean-François, additional, Desautels, Alex, additional, Montplaisir, Jacques Y., additional, Postuma, Ronald B., additional, Rouleau, Guy A., additional, and Gan-Or, Ziv, additional

Published
2019
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45. Microfluidic flow confinement to avoid chemotaxis-based upstream growth in a biofilm flow cell reactor

Author

Asayesh, Farnaz, Zarabadi, Mirpouyan, Babaei Aznaveh, Nahid, Greener, Jesse, Asayesh, Farnaz, Zarabadi, Mirpouyan, Babaei Aznaveh, Nahid, and Greener, Jesse

Abstract

Introduction of a bacterial inoculant into a chemostat bioreactor can lead to unwanted contamination of upstream elements via chemotaxis. This can result in biofilm growth in connective tubing, valves and even the medium source reservoir itself, thus complicating the conditions of the applied liquid phase and impeding proper chemostat functionality. Applied to biofilm forming Pseudomonas fluorescens bacteria, we tested two different microfluidic flow confinement methods designed to impede upstream contamination. The first isolated biofilm growth from the relatively stagnant zones within the microchannel corners, and in the second a flow enhancement element was introduced to increase flow velocities and shear forces. Both methods showed improvement over a control design, but flow enhancement showed the best performance by delaying or preventing bacterial contamination of upstream elements, ensuring stability of the applied liquid media conditions for the entire duration of the experiments. This simple passive element has the potential for wide use as it is easy to implement and can be optimised for different experimental requirements.

Published
2018

46. Targeted sequencing of Parkinson's disease loci genes highlights SYT11, FGF20 and other associations.

Author

Rudakou, Uladzislau, Yu, Eric, Krohn, Lynne, Ruskey, Jennifer A, Asayesh, Farnaz, Dauvilliers, Yves, Spiegelman, Dan, Greenbaum, Lior, Fahn, Stanley, Waters, Cheryl H, Dupré, Nicolas, Rouleau, Guy A, Hassin-Baer, Sharon, Fon, Edward A, Alcalay, Roy N, and Gan-Or, Ziv

Subjects
PARKINSON'S disease, GENES, MOLECULAR probes, LINKAGE disequilibrium, PROMOTERS (Genetics), GENE targeting, RESEARCH, GENETIC mutation, GROWTH factors, RESEARCH methodology, GENETIC polymorphisms, MEDICAL cooperation, EVALUATION research, COMPARATIVE studies, DISEASE susceptibility, RESEARCH funding, CALCIUM-binding proteins
Abstract

Genome-wide association studies (GWAS) have identified numerous loci associated with Parkinson's disease. The specific genes and variants that drive the associations within the vast majority of these loci are unknown. We aimed to perform a comprehensive analysis of selected genes to determine the potential role of rare and common genetic variants within these loci. We fully sequenced 32 genes from 25 loci previously associated with Parkinson's disease in 2657 patients and 3647 controls from three cohorts. Capture was done using molecular inversion probes targeting the exons, exon-intron boundaries and untranslated regions (UTRs) of the genes of interest, followed by sequencing. Quality control was performed to include only high-quality variants. We examined the role of rare variants (minor allele frequency < 0.01) using optimized sequence Kernel association tests. The association of common variants was estimated using regression models adjusted for age, sex and ethnicity as required in each cohort, followed by a meta-analysis. After Bonferroni correction, we identified a burden of rare variants in SYT11, FGF20 and GCH1 associated with Parkinson's disease. Nominal associations were identified in 21 additional genes. Previous reports suggested that the SYT11 GWAS association is driven by variants in the nearby GBA gene. However, the association of SYT11 was mainly driven by a rare 3' UTR variant (rs945006601) and was independent of GBA variants (P = 5.23 × 10-5 after exclusion of all GBA variant carriers). The association of FGF20 was driven by a rare 5' UTR variant (rs1034608171) located in the promoter region. The previously reported association of GCH1 with Parkinson's disease is driven by rare non-synonymous variants, some of which are known to cause dopamine-responsive dystonia. We also identified two LRRK2 variants, p.Arg793Met and p.Gln1353Lys, in 10 and eight controls, respectively, but not in patients. We identified common variants associated with Parkinson's disease in MAPT, TMEM175, BST1, SNCA and GPNMB, which are all in strong linkage disequilibrium with known GWAS hits in their respective loci. A common coding PM20D1 variant, p.Ile149Val, was nominally associated with reduced risk of Parkinson's disease (odds ratio 0.73, 95% confidence interval 0.60-0.89, P = 1.161 × 10-3). This variant is not in linkage disequilibrium with the top GWAS hits within this locus and may represent a novel association. These results further demonstrate the importance of fine mapping of GWAS loci, and suggest that SYT11, FGF20, and potentially PM20D1, BST1 and GPNMB should be considered for future studies as possible Parkinson's disease-related genes. [ABSTRACT FROM AUTHOR]

Published
2021
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47. Comprehensive Analysis of Familial Parkinsonism Genes in Rapid-Eye-Movement Sleep Behavior Disorder.

Author

Mufti, Kheireddin, Rudakou, Uladzislau, Yu, Eric, Krohn, Lynne, Ruskey, Jennifer A., Asayesh, Farnaz, Laurent, Sandra B., Spiegelman, Dan, Arnulf, Isabelle, Hu, Michele T.M., Montplaisir, Jacques Y., Gagnon, Jean‐François, Desautels, Alex, Dauvilliers, Yves, Gigli, Gian Luigi, Valente, Mariarosaria, Janes, Francesco, Högl, Birgit, Stefani, Ambra, and Holzknecht, Evi

Abstract

Background: There is only partial overlap in the genetic background of isolated rapid-eye-movement sleep behavior disorder (iRBD) and Parkinson's disease (PD).Objective: To examine the role of autosomal dominant and recessive PD or atypical parkinsonism genes in the risk of iRBD.Methods: Ten genes, comprising the recessive genes PRKN, DJ-1 (PARK7), PINK1, VPS13C, ATP13A2, FBXO7, and PLA2G6 and the dominant genes LRRK2, GCH1, and VPS35, were fully sequenced in 1039 iRBD patients and 1852 controls of European ancestry, followed by association tests.Results: We found no association between rare heterozygous variants in the tested genes and risk of iRBD. Several homozygous and compound heterozygous carriers were identified, yet there was no overrepresentation in iRBD patients versus controls.Conclusion: Our results do not support a major role for variants in these genes in the risk of iRBD. © 2020 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Published
2021
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48. Analysis of Heterozygous PRKN Variants and Copy‐Number Variations in Parkinson's Disease.

Author

Yu, Eric, Rudakou, Uladzislau, Krohn, Lynne, Mufti, Kheireddin, Ruskey, Jennifer A., Asayesh, Farnaz, Estiar, Mehrdad A., Spiegelman, Dan, Surface, Matthew, Fahn, Stanley, Waters, Cheryl H., Greenbaum, Lior, Espay, Alberto J., Dauvilliers, Yves, Dupré, Nicolas, Rouleau, Guy A., Hassin‐Baer, Sharon, Fon, Edward A., Alcalay, Roy N., and Gan‐Or, Ziv

Abstract

Background: Biallelic PRKN mutation carriers with Parkinson's disease (PD) typically have an earlier disease onset, slow disease progression, and, often, different neuropathology compared to sporadic PD patients. However, the role of heterozygous PRKN variants in the risk of PD is controversial. Objectives: Our aim was to examine the association between heterozygous PRKN variants, including single‐nucleotide variants and copy‐number variations (CNVs), and PD. Methods: We fully sequenced PRKN in 2809 PD patients and 3629 healthy controls, including 1965 late‐onset (63.97 ± 7.79 years, 63% men) and 553 early‐onset PD patients (43.33 ± 6.59 years, 68% men). PRKN was sequenced using targeted next‐generation sequencing with molecular inversion probes. CNVs were identified using a combination of multiplex ligation‐dependent probe amplification and ExomeDepth. To examine whether rare heterozygous single‐nucleotide variants and CNVs in PRKN are associated with PD risk and onset, we used optimized sequence kernel association tests and regression models. Results: We did not find any associations between all types of PRKN variants and risk of PD. Pathogenic and likely‐pathogenic heterozygous single‐nucleotide variants and CNVs were less common among PD patients (1.52%) than among controls (1.8%, false discovery rate‐corrected P = 0.55). No associations with age at onset and in stratified analyses were found. Conclusions: Heterozygous single‐nucleotide variants and CNVs in PRKN are not associated with PD. Molecular inversion probes allow for rapid and cost‐effective detection of all types of PRKN variants, which may be useful for pretrial screening and for clinical and basic science studies targeting specifically PRKN patients. © 2020 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Published
2021
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49. variants in REM sleep behavior disorder: A multicenter study.

Author

Krohn, Lynne, Ruskey, Jennifer A., Rudakou, Uladzislau, Leveille, Etienne, Asayesh, Farnaz, Hu, Michele T. M., Arnulf, Isabelle, Dauvilliers, Yves, Högl, Birgit, Stefani, Ambra, Monaca, Christelle Charley, Abril, Beatriz, Plazzi, Giuseppe, Antelmi, Elena, Ferini-Strambi, Luigi, Heidbreder, Anna, Boeve, Bradley F., Espay, Alberto J., De Cock, Valérie Cochen, and Mollenhauer, Brit

Published
2020
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