Moving beyond neurons
Parkinson's disease (PD), with its characteristic loss of nigrostriatal dopaminergic neurons and deposition of α-synuclein in neurons, is often considered a neuronal disorder. However, in recent years substantial evidence has emerged to implicate glial cell types, such as astrocytes and microgl...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | artículo |
| Fecha de publicación: | 2019 |
| País: | España |
| Recursos: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:223586 |
| Acesso em linha: | https://ddd.uab.cat/record/223586 https://dx.doi.org/urn:doi:10.1038/s41531-019-0076-6 |
| Access Level: | acceso abierto |
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oai:ddd.uab.cat:223586 |
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España |
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| dc.title.none.fl_str_mv |
Moving beyond neurons the role of cell type-specific gene regulation in Parkinson's disease heritability |
| title |
Moving beyond neurons |
| spellingShingle |
Moving beyond neurons Reynolds, Regina H.|||0000-0001-6470-7919 |
| title_short |
Moving beyond neurons |
| title_full |
Moving beyond neurons |
| title_fullStr |
Moving beyond neurons |
| title_full_unstemmed |
Moving beyond neurons |
| title_sort |
Moving beyond neurons |
| dc.creator.none.fl_str_mv |
Reynolds, Regina H.|||0000-0001-6470-7919 Botía, Juan A.|||0000-0002-6992-598X Nalls, Mike A. Noyce, Alastair J. Nicolas, Aude Cookson, Mark R. Bandres-Ciga, Sara|||0000-0003-0056-1361 Gibbs, J. Raphael|||0000-0002-6985-0658 Hernandez, Dena G.|||0000-0002-0188-9927 Singleton, Andrew B.|||0000-0001-5606-700X Reed, Xylena Leonard, Hampton L.|||0000-0003-2390-8110 Blauwendraat, Cornelis|||0000-0001-9358-8111 Faghri, Faraz Bras, Jose|||0000-0001-8186-0333 Guerreiro, Rita|||0000-0001-5879-3486 Tucci, Arianna|||0000-0001-5644-0070 Kia, Demis A. Houlden, Henry|||0000-0002-2866-7777 Plun-Favreau, Helen Mok, Kin Ying|||0000-0003-3145-880X Wood, Nicholas W.|||0000-0002-9500-3348 Lovering, Ruth Caroline|||0000-0002-9791-0064 R'Bibo, Lea Rizig, Mie|||0000-0003-2420-4449 Chelban, Viorica|||0000-0002-5817-6290 Trabzuni, Daniah|||0000-0003-4826-9570 Tan, Manuela|||0000-0001-5835-669X Morris, Huw|||0000-0002-5473-3774 Middlehurst, Ben Quinn, John Billingsley, Kimberley Holmans, Peter|||0000-0003-0870-9412 Kinghorn, Kerri J.|||0000-0003-2048-4332 Lewis, Patrick|||0000-0003-4537-0489 Escott-Price, Valentina|||0000-0003-1784-5483 Williams, Nigel Foltynie, Thomas|||0000-0003-0752-1813 Brice, Alexis|||0000-0002-0941-3990 Danjou, Fabrice|||0000-0002-4976-2327 Lesage, Suzanne Corvol, Jean-Christophe|||0000-0001-7325-0199 Martinez, Maria Giri, Anamika Schulte, Claudia|||0000-0003-4006-1265 Brockmann, Kathrin|||0000-0002-7515-8596 Simón-Sánchez, Javier Heutink, Peter|||0000-0001-5218-1737 Gasser, Thomas|||0000-0003-4882-2647 Rizzu, Patrizia Sharma, Manu Shulman, Joshua M. Robak, Laurie Lubbe, Steven Mencacci, Niccolò Emanuele|||0000-0003-3383-9665 Finkbeiner, Steven Lungu, Codrin Scholz, Sonja|||0000-0002-6623-0429 Gan-Or, Ziv|||0000-0003-0332-234X Rouleau, Guy A.|||0000-0001-8403-1418 Krohan, Lynne van Hilten, Jacobus J. Marinus, Johan Adarmes-Gómez, A.D.|||0000-0002-1337-9289 Bernal-Bernal, Inmaculada Bonilla-Toribio, Marta Buiza-Rueda, Dolores|||0000-0002-3504-9299 Carrillo, Fátima Carrión-Claro, M. Mir, Pablo|||0000-0003-1656-302X Gómez-Garre, Pilar|||0000-0002-0437-6182 Jesús, Silvia Labrador-Espinosa, Miguel A.|||0000-0003-3576-1777 Macías-García, Daniel|||0000-0002-4822-1529 Vargas-González, Laura Méndez-del-Barrio, Carlota Periñán-Tocino, Teresa Tejera-Parrado, Cristina|||0000-0001-8001-5621 Diez-Fairen, Monica|||0000-0003-1882-0309 Aguilar Barberà, Miquel Alvarez, Ignacio|||0000-0002-8537-3935 Boungiorno, M. T. Carcel, Maria Pastor, Pau|||0000-0002-7493-8777 Tartari, Juan Pablo Alvarez, Victoria|||0000-0002-1916-2523 González, Manel Menéndez Blázquez Estrada, Marta|||0000-0003-3348-9992 Garcia, Ciara Suarez-Sanmartin, Esther Barrero, Francisco Javier Rezola, Elisabet Mondragon Yarza, Jesús Alberto Bergareche Gorostidi Pagola, Ana de Munain Arregui, Adolfo López Ruiz-Martínez, J. Cerdan, Debora|||0000-0001-5408-691X Duarte, J. Clarimón, Jordi|||0000-0002-6824-6942 Dols Icardo, Oriol|||0000-0003-2656-8748 Infante, J. Marín, J. Kulisevsky, Jaime|||0000-0003-4870-1431 Pagonabarraga Mora, Javier|||0000-0002-3248-704X Gonzalez-Aramburu, Isabel|||0000-0002-3696-4093 Rodriguez, A. S. Sierra, M. Duran, Raquel Ruz, C. Vives, Francisco Escamilla Sevilla, Francisco|||0000-0003-2149-2668 Mínguez, A. Cámara, Ana|||0000-0002-8005-9461 Compta, Yaroslau|||0000-0001-6443-0104 Ezquerra, Mario|||0000-0003-3246-6641 Marti, M. J. Fernández, M. Muñoz García, José Esteban|||0000-0002-0986-1291 Fernández-Santiago, Rubén|||0000-0002-4582-0702 Tolosa, E. Valldeoriola, F. García-Ruiz, P. Heredia, M. J. G. Errazquin, F. P. Hoenicka, J. Jiménez-Escrig, Adriano|||0000-0002-4927-1886 Martínez-Castrillo, Juan Carlos|||0000-0001-7744-6850 Lopez-Sendon, J. L. Torres, I. M. Tabernero, Cesar Vela, Lydia|||0000-0001-6663-395X Zimprich, Alexander|||0000-0002-1668-5177 Pihlstrom, L. Koks, S. Taba, Pille|||0000-0002-1315-1065 Majamaa, K. Siitonen, A. Okubadejo, N. U. Ojo, O. O. Pitcher, T. Anderson, T. Bentley, S. Fowdar, J. Mellick, G. Dalrymple-Alford, J. Henders, Anjali K. Kassam, I. Montgomery, G. Sidorenko, J. Zhang, Futao Xue, Angli Vallerga, Costanza L. Wallace, Leanne Wray, N. R. Yang, J. Visscher, P. M. Gratten, J. Silburn, P. A. Halliday, G. Hickie, Ian B.|||0000-0001-8832-9895 Kwok, John B.J. Lewis, S. Kennedy, M. Pearson, J. Hardy, J. Gagliano Taliun, Sarah A.|||0000-0003-1306-1868 Ryten, Mina |
| author |
Reynolds, Regina H.|||0000-0001-6470-7919 |
| author_facet |
Reynolds, Regina H.|||0000-0001-6470-7919 Botía, Juan A.|||0000-0002-6992-598X Nalls, Mike A. Noyce, Alastair J. Nicolas, Aude Cookson, Mark R. Bandres-Ciga, Sara|||0000-0003-0056-1361 Gibbs, J. Raphael|||0000-0002-6985-0658 Hernandez, Dena G.|||0000-0002-0188-9927 Singleton, Andrew B.|||0000-0001-5606-700X Reed, Xylena Leonard, Hampton L.|||0000-0003-2390-8110 Blauwendraat, Cornelis|||0000-0001-9358-8111 Faghri, Faraz Bras, Jose|||0000-0001-8186-0333 Guerreiro, Rita|||0000-0001-5879-3486 Tucci, Arianna|||0000-0001-5644-0070 Kia, Demis A. Houlden, Henry|||0000-0002-2866-7777 Plun-Favreau, Helen Mok, Kin Ying|||0000-0003-3145-880X Wood, Nicholas W.|||0000-0002-9500-3348 Lovering, Ruth Caroline|||0000-0002-9791-0064 R'Bibo, Lea Rizig, Mie|||0000-0003-2420-4449 Chelban, Viorica|||0000-0002-5817-6290 Trabzuni, Daniah|||0000-0003-4826-9570 Tan, Manuela|||0000-0001-5835-669X Morris, Huw|||0000-0002-5473-3774 Middlehurst, Ben Quinn, John Billingsley, Kimberley Holmans, Peter|||0000-0003-0870-9412 Kinghorn, Kerri J.|||0000-0003-2048-4332 Lewis, Patrick|||0000-0003-4537-0489 Escott-Price, Valentina|||0000-0003-1784-5483 Williams, Nigel Foltynie, Thomas|||0000-0003-0752-1813 Brice, Alexis|||0000-0002-0941-3990 Danjou, Fabrice|||0000-0002-4976-2327 Lesage, Suzanne Corvol, Jean-Christophe|||0000-0001-7325-0199 Martinez, Maria Giri, Anamika Schulte, Claudia|||0000-0003-4006-1265 Brockmann, Kathrin|||0000-0002-7515-8596 Simón-Sánchez, Javier Heutink, Peter|||0000-0001-5218-1737 Gasser, Thomas|||0000-0003-4882-2647 Rizzu, Patrizia Sharma, Manu Shulman, Joshua M. Robak, Laurie Lubbe, Steven Mencacci, Niccolò Emanuele|||0000-0003-3383-9665 Finkbeiner, Steven Lungu, Codrin Scholz, Sonja|||0000-0002-6623-0429 Gan-Or, Ziv|||0000-0003-0332-234X Rouleau, Guy A.|||0000-0001-8403-1418 Krohan, Lynne van Hilten, Jacobus J. Marinus, Johan Adarmes-Gómez, A.D.|||0000-0002-1337-9289 Bernal-Bernal, Inmaculada Bonilla-Toribio, Marta Buiza-Rueda, Dolores|||0000-0002-3504-9299 Carrillo, Fátima Carrión-Claro, M. Mir, Pablo|||0000-0003-1656-302X Gómez-Garre, Pilar|||0000-0002-0437-6182 Jesús, Silvia Labrador-Espinosa, Miguel A.|||0000-0003-3576-1777 Macías-García, Daniel|||0000-0002-4822-1529 Vargas-González, Laura Méndez-del-Barrio, Carlota Periñán-Tocino, Teresa Tejera-Parrado, Cristina|||0000-0001-8001-5621 Diez-Fairen, Monica|||0000-0003-1882-0309 Aguilar Barberà, Miquel Alvarez, Ignacio|||0000-0002-8537-3935 Boungiorno, M. T. Carcel, Maria Pastor, Pau|||0000-0002-7493-8777 Tartari, Juan Pablo Alvarez, Victoria|||0000-0002-1916-2523 González, Manel Menéndez Blázquez Estrada, Marta|||0000-0003-3348-9992 Garcia, Ciara Suarez-Sanmartin, Esther Barrero, Francisco Javier Rezola, Elisabet Mondragon Yarza, Jesús Alberto Bergareche Gorostidi Pagola, Ana de Munain Arregui, Adolfo López Ruiz-Martínez, J. Cerdan, Debora|||0000-0001-5408-691X Duarte, J. Clarimón, Jordi|||0000-0002-6824-6942 Dols Icardo, Oriol|||0000-0003-2656-8748 Infante, J. Marín, J. Kulisevsky, Jaime|||0000-0003-4870-1431 Pagonabarraga Mora, Javier|||0000-0002-3248-704X Gonzalez-Aramburu, Isabel|||0000-0002-3696-4093 Rodriguez, A. S. Sierra, M. Duran, Raquel Ruz, C. Vives, Francisco Escamilla Sevilla, Francisco|||0000-0003-2149-2668 Mínguez, A. Cámara, Ana|||0000-0002-8005-9461 Compta, Yaroslau|||0000-0001-6443-0104 Ezquerra, Mario|||0000-0003-3246-6641 Marti, M. J. Fernández, M. Muñoz García, José Esteban|||0000-0002-0986-1291 Fernández-Santiago, Rubén|||0000-0002-4582-0702 Tolosa, E. Valldeoriola, F. García-Ruiz, P. Heredia, M. J. G. Errazquin, F. P. Hoenicka, J. Jiménez-Escrig, Adriano|||0000-0002-4927-1886 Martínez-Castrillo, Juan Carlos|||0000-0001-7744-6850 Lopez-Sendon, J. L. Torres, I. M. Tabernero, Cesar Vela, Lydia|||0000-0001-6663-395X Zimprich, Alexander|||0000-0002-1668-5177 Pihlstrom, L. Koks, S. Taba, Pille|||0000-0002-1315-1065 Majamaa, K. Siitonen, A. Okubadejo, N. U. Ojo, O. O. Pitcher, T. Anderson, T. Bentley, S. Fowdar, J. Mellick, G. Dalrymple-Alford, J. Henders, Anjali K. Kassam, I. Montgomery, G. Sidorenko, J. Zhang, Futao Xue, Angli Vallerga, Costanza L. Wallace, Leanne Wray, N. R. Yang, J. Visscher, P. M. Gratten, J. Silburn, P. A. Halliday, G. Hickie, Ian B.|||0000-0001-8832-9895 Kwok, John B.J. Lewis, S. Kennedy, M. Pearson, J. Hardy, J. Gagliano Taliun, Sarah A.|||0000-0003-1306-1868 Ryten, Mina |
| author_role |
author |
| author2 |
Botía, Juan A.|||0000-0002-6992-598X Nalls, Mike A. Noyce, Alastair J. Nicolas, Aude Cookson, Mark R. Bandres-Ciga, Sara|||0000-0003-0056-1361 Gibbs, J. Raphael|||0000-0002-6985-0658 Hernandez, Dena G.|||0000-0002-0188-9927 Singleton, Andrew B.|||0000-0001-5606-700X Reed, Xylena Leonard, Hampton L.|||0000-0003-2390-8110 Blauwendraat, Cornelis|||0000-0001-9358-8111 Faghri, Faraz Bras, Jose|||0000-0001-8186-0333 Guerreiro, Rita|||0000-0001-5879-3486 Tucci, Arianna|||0000-0001-5644-0070 Kia, Demis A. Houlden, Henry|||0000-0002-2866-7777 Plun-Favreau, Helen Mok, Kin Ying|||0000-0003-3145-880X Wood, Nicholas W.|||0000-0002-9500-3348 Lovering, Ruth Caroline|||0000-0002-9791-0064 R'Bibo, Lea Rizig, Mie|||0000-0003-2420-4449 Chelban, Viorica|||0000-0002-5817-6290 Trabzuni, Daniah|||0000-0003-4826-9570 Tan, Manuela|||0000-0001-5835-669X Morris, Huw|||0000-0002-5473-3774 Middlehurst, Ben Quinn, John Billingsley, Kimberley Holmans, Peter|||0000-0003-0870-9412 Kinghorn, Kerri J.|||0000-0003-2048-4332 Lewis, Patrick|||0000-0003-4537-0489 Escott-Price, Valentina|||0000-0003-1784-5483 Williams, Nigel Foltynie, Thomas|||0000-0003-0752-1813 Brice, Alexis|||0000-0002-0941-3990 Danjou, Fabrice|||0000-0002-4976-2327 Lesage, Suzanne Corvol, Jean-Christophe|||0000-0001-7325-0199 Martinez, Maria Giri, Anamika Schulte, Claudia|||0000-0003-4006-1265 Brockmann, Kathrin|||0000-0002-7515-8596 Simón-Sánchez, Javier Heutink, Peter|||0000-0001-5218-1737 Gasser, Thomas|||0000-0003-4882-2647 Rizzu, Patrizia Sharma, Manu Shulman, Joshua M. Robak, Laurie Lubbe, Steven Mencacci, Niccolò Emanuele|||0000-0003-3383-9665 Finkbeiner, Steven Lungu, Codrin Scholz, Sonja|||0000-0002-6623-0429 Gan-Or, Ziv|||0000-0003-0332-234X Rouleau, Guy A.|||0000-0001-8403-1418 Krohan, Lynne van Hilten, Jacobus J. Marinus, Johan Adarmes-Gómez, A.D.|||0000-0002-1337-9289 Bernal-Bernal, Inmaculada Bonilla-Toribio, Marta Buiza-Rueda, Dolores|||0000-0002-3504-9299 Carrillo, Fátima Carrión-Claro, M. Mir, Pablo|||0000-0003-1656-302X Gómez-Garre, Pilar|||0000-0002-0437-6182 Jesús, Silvia Labrador-Espinosa, Miguel A.|||0000-0003-3576-1777 Macías-García, Daniel|||0000-0002-4822-1529 Vargas-González, Laura Méndez-del-Barrio, Carlota Periñán-Tocino, Teresa Tejera-Parrado, Cristina|||0000-0001-8001-5621 Diez-Fairen, Monica|||0000-0003-1882-0309 Aguilar Barberà, Miquel Alvarez, Ignacio|||0000-0002-8537-3935 Boungiorno, M. T. Carcel, Maria Pastor, Pau|||0000-0002-7493-8777 Tartari, Juan Pablo Alvarez, Victoria|||0000-0002-1916-2523 González, Manel Menéndez Blázquez Estrada, Marta|||0000-0003-3348-9992 Garcia, Ciara Suarez-Sanmartin, Esther Barrero, Francisco Javier Rezola, Elisabet Mondragon Yarza, Jesús Alberto Bergareche Gorostidi Pagola, Ana de Munain Arregui, Adolfo López Ruiz-Martínez, J. Cerdan, Debora|||0000-0001-5408-691X Duarte, J. Clarimón, Jordi|||0000-0002-6824-6942 Dols Icardo, Oriol|||0000-0003-2656-8748 Infante, J. Marín, J. Kulisevsky, Jaime|||0000-0003-4870-1431 Pagonabarraga Mora, Javier|||0000-0002-3248-704X Gonzalez-Aramburu, Isabel|||0000-0002-3696-4093 Rodriguez, A. S. Sierra, M. Duran, Raquel Ruz, C. Vives, Francisco Escamilla Sevilla, Francisco|||0000-0003-2149-2668 Mínguez, A. Cámara, Ana|||0000-0002-8005-9461 Compta, Yaroslau|||0000-0001-6443-0104 Ezquerra, Mario|||0000-0003-3246-6641 Marti, M. J. Fernández, M. Muñoz García, José Esteban|||0000-0002-0986-1291 Fernández-Santiago, Rubén|||0000-0002-4582-0702 Tolosa, E. Valldeoriola, F. García-Ruiz, P. Heredia, M. J. G. Errazquin, F. P. Hoenicka, J. Jiménez-Escrig, Adriano|||0000-0002-4927-1886 Martínez-Castrillo, Juan Carlos|||0000-0001-7744-6850 Lopez-Sendon, J. L. Torres, I. M. Tabernero, Cesar Vela, Lydia|||0000-0001-6663-395X Zimprich, Alexander|||0000-0002-1668-5177 Pihlstrom, L. Koks, S. Taba, Pille|||0000-0002-1315-1065 Majamaa, K. Siitonen, A. Okubadejo, N. U. Ojo, O. O. Pitcher, T. Anderson, T. Bentley, S. Fowdar, J. Mellick, G. Dalrymple-Alford, J. Henders, Anjali K. Kassam, I. Montgomery, G. Sidorenko, J. Zhang, Futao Xue, Angli Vallerga, Costanza L. Wallace, Leanne Wray, N. R. Yang, J. Visscher, P. M. Gratten, J. Silburn, P. A. Halliday, G. Hickie, Ian B.|||0000-0001-8832-9895 Kwok, John B.J. Lewis, S. Kennedy, M. Pearson, J. Hardy, J. Gagliano Taliun, Sarah A.|||0000-0003-1306-1868 Ryten, Mina |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universitat Autònoma de Barcelona |
| description |
Parkinson's disease (PD), with its characteristic loss of nigrostriatal dopaminergic neurons and deposition of α-synuclein in neurons, is often considered a neuronal disorder. However, in recent years substantial evidence has emerged to implicate glial cell types, such as astrocytes and microglia. In this study, we used stratified LD score regression and expression-weighted cell-type enrichment together with several brain-related and cell-type-specific genomic annotations to connect human genomic PD findings to specific brain cell types. We found that PD heritability attributable to common variation does not enrich in global and regional brain annotations or brain-related cell-type-specific annotations. Likewise, we found no enrichment of PD susceptibility genes in brain-related cell types. In contrast, we demonstrated a significant enrichment of PD heritability in a curated lysosomal gene set highly expressed in astrocytic, microglial, and oligodendrocyte subtypes, and in LoF-intolerant genes, which were found highly expressed in almost all tested cellular subtypes. Our results suggest that PD risk loci do not lie in specific cell types or individual brain regions, but rather in global cellular processes detectable across several cell types. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2 2019-01-01 2019 2019-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://ddd.uab.cat/record/223586 https://dx.doi.org/urn:doi:10.1038/s41531-019-0076-6 |
| url |
https://ddd.uab.cat/record/223586 https://dx.doi.org/urn:doi:10.1038/s41531-019-0076-6 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.source.none.fl_str_mv |
reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona |
| instname_str |
Universitat Autònoma de Barcelona |
| reponame_str |
Dipòsit Digital de Documents de la UAB |
| collection |
Dipòsit Digital de Documents de la UAB |
| repository.name.fl_str_mv |
|
| repository.mail.fl_str_mv |
|
| _version_ |
1869405105108811776 |
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Moving beyond neuronsthe role of cell type-specific gene regulation in Parkinson's disease heritabilityReynolds, Regina H.|||0000-0001-6470-7919Botía, Juan A.|||0000-0002-6992-598XNalls, Mike A.Noyce, Alastair J.Nicolas, AudeCookson, Mark R.Bandres-Ciga, Sara|||0000-0003-0056-1361Gibbs, J. Raphael|||0000-0002-6985-0658Hernandez, Dena G.|||0000-0002-0188-9927Singleton, Andrew B.|||0000-0001-5606-700XReed, XylenaLeonard, Hampton L.|||0000-0003-2390-8110Blauwendraat, Cornelis|||0000-0001-9358-8111Faghri, FarazBras, Jose|||0000-0001-8186-0333Guerreiro, Rita|||0000-0001-5879-3486Tucci, Arianna|||0000-0001-5644-0070Kia, Demis A.Houlden, Henry|||0000-0002-2866-7777Plun-Favreau, HelenMok, Kin Ying|||0000-0003-3145-880XWood, Nicholas W.|||0000-0002-9500-3348Lovering, Ruth Caroline|||0000-0002-9791-0064R'Bibo, LeaRizig, Mie|||0000-0003-2420-4449Chelban, Viorica|||0000-0002-5817-6290Trabzuni, Daniah|||0000-0003-4826-9570Tan, Manuela|||0000-0001-5835-669XMorris, Huw|||0000-0002-5473-3774Middlehurst, BenQuinn, JohnBillingsley, KimberleyHolmans, Peter|||0000-0003-0870-9412Kinghorn, Kerri J.|||0000-0003-2048-4332Lewis, Patrick|||0000-0003-4537-0489Escott-Price, Valentina|||0000-0003-1784-5483Williams, NigelFoltynie, Thomas|||0000-0003-0752-1813Brice, Alexis|||0000-0002-0941-3990Danjou, Fabrice|||0000-0002-4976-2327Lesage, SuzanneCorvol, Jean-Christophe|||0000-0001-7325-0199Martinez, MariaGiri, AnamikaSchulte, Claudia|||0000-0003-4006-1265Brockmann, Kathrin|||0000-0002-7515-8596Simón-Sánchez, JavierHeutink, Peter|||0000-0001-5218-1737Gasser, Thomas|||0000-0003-4882-2647Rizzu, PatriziaSharma, ManuShulman, Joshua M.Robak, LaurieLubbe, StevenMencacci, Niccolò Emanuele|||0000-0003-3383-9665Finkbeiner, StevenLungu, CodrinScholz, Sonja|||0000-0002-6623-0429Gan-Or, Ziv|||0000-0003-0332-234XRouleau, Guy A.|||0000-0001-8403-1418Krohan, Lynnevan Hilten, Jacobus J.Marinus, JohanAdarmes-Gómez, A.D.|||0000-0002-1337-9289Bernal-Bernal, InmaculadaBonilla-Toribio, MartaBuiza-Rueda, Dolores|||0000-0002-3504-9299Carrillo, FátimaCarrión-Claro, M.Mir, Pablo|||0000-0003-1656-302XGómez-Garre, Pilar|||0000-0002-0437-6182Jesús, SilviaLabrador-Espinosa, Miguel A.|||0000-0003-3576-1777Macías-García, Daniel|||0000-0002-4822-1529Vargas-González, LauraMéndez-del-Barrio, CarlotaPeriñán-Tocino, TeresaTejera-Parrado, Cristina|||0000-0001-8001-5621Diez-Fairen, Monica|||0000-0003-1882-0309Aguilar Barberà, MiquelAlvarez, Ignacio|||0000-0002-8537-3935Boungiorno, M. T.Carcel, MariaPastor, Pau|||0000-0002-7493-8777Tartari, Juan PabloAlvarez, Victoria|||0000-0002-1916-2523González, Manel MenéndezBlázquez Estrada, Marta|||0000-0003-3348-9992Garcia, CiaraSuarez-Sanmartin, EstherBarrero, Francisco JavierRezola, Elisabet MondragonYarza, Jesús Alberto BergarecheGorostidi Pagola, Anade Munain Arregui, Adolfo LópezRuiz-Martínez, J.Cerdan, Debora|||0000-0001-5408-691XDuarte, J.Clarimón, Jordi|||0000-0002-6824-6942Dols Icardo, Oriol|||0000-0003-2656-8748Infante, J.Marín, J.Kulisevsky, Jaime|||0000-0003-4870-1431Pagonabarraga Mora, Javier|||0000-0002-3248-704XGonzalez-Aramburu, Isabel|||0000-0002-3696-4093Rodriguez, A. S.Sierra, M.Duran, RaquelRuz, C.Vives, FranciscoEscamilla Sevilla, Francisco|||0000-0003-2149-2668Mínguez, A.Cámara, Ana|||0000-0002-8005-9461Compta, Yaroslau|||0000-0001-6443-0104Ezquerra, Mario|||0000-0003-3246-6641Marti, M. J.Fernández, M.Muñoz García, José Esteban|||0000-0002-0986-1291Fernández-Santiago, Rubén|||0000-0002-4582-0702Tolosa, E.Valldeoriola, F.García-Ruiz, P.Heredia, M. J. G.Errazquin, F. P.Hoenicka, J.Jiménez-Escrig, Adriano|||0000-0002-4927-1886Martínez-Castrillo, Juan Carlos|||0000-0001-7744-6850Lopez-Sendon, J. L.Torres, I. M.Tabernero, CesarVela, Lydia|||0000-0001-6663-395XZimprich, Alexander|||0000-0002-1668-5177Pihlstrom, L.Koks, S.Taba, Pille|||0000-0002-1315-1065Majamaa, K.Siitonen, A.Okubadejo, N. U.Ojo, O. O.Pitcher, T.Anderson, T.Bentley, S.Fowdar, J.Mellick, G.Dalrymple-Alford, J.Henders, Anjali K.Kassam, I.Montgomery, G.Sidorenko, J.Zhang, FutaoXue, AngliVallerga, Costanza L.Wallace, LeanneWray, N. R.Yang, J.Visscher, P. M.Gratten, J.Silburn, P. A.Halliday, G.Hickie, Ian B.|||0000-0001-8832-9895Kwok, John B.J.Lewis, S.Kennedy, M.Pearson, J.Hardy, J.Gagliano Taliun, Sarah A.|||0000-0003-1306-1868Ryten, MinaParkinson's disease (PD), with its characteristic loss of nigrostriatal dopaminergic neurons and deposition of α-synuclein in neurons, is often considered a neuronal disorder. However, in recent years substantial evidence has emerged to implicate glial cell types, such as astrocytes and microglia. In this study, we used stratified LD score regression and expression-weighted cell-type enrichment together with several brain-related and cell-type-specific genomic annotations to connect human genomic PD findings to specific brain cell types. We found that PD heritability attributable to common variation does not enrich in global and regional brain annotations or brain-related cell-type-specific annotations. Likewise, we found no enrichment of PD susceptibility genes in brain-related cell types. In contrast, we demonstrated a significant enrichment of PD heritability in a curated lysosomal gene set highly expressed in astrocytic, microglial, and oligodendrocyte subtypes, and in LoF-intolerant genes, which were found highly expressed in almost all tested cellular subtypes. Our results suggest that PD risk loci do not lie in specific cell types or individual brain regions, but rather in global cellular processes detectable across several cell types.Universitat Autònoma de Barcelona 22019-01-0120192019-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/223586https://dx.doi.org/urn:doi:10.1038/s41531-019-0076-6reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2235862026-06-06T12:50:31Z |
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