Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease
Perivascular space (PVS) burden is an emerging, poorly understood, magnetic resonance imaging marker of cerebral small vessel disease, a leading cause of stroke and dementia. Genome-wide association studies in up to 40,095 participants (18 population-based cohorts, 66.3 ± 8.6 yr, 96.9% European ance...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:280931 |
| Acceso en línea: | https://ddd.uab.cat/record/280931 https://dx.doi.org/urn:doi:10.1038/s41591-023-02268-w |
| Access Level: | acceso abierto |
| Palabra clave: | Neurology Stroke Genome-wide association studies |
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oai:ddd.uab.cat:280931 |
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| network_name_str |
España |
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| dc.title.none.fl_str_mv |
Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease |
| title |
Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease |
| spellingShingle |
Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease Duperron, Marie-Gabrielle|||0000-0001-7408-7792 Neurology Stroke Genome-wide association studies |
| title_short |
Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease |
| title_full |
Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease |
| title_fullStr |
Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease |
| title_full_unstemmed |
Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease |
| title_sort |
Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease |
| dc.creator.none.fl_str_mv |
Duperron, Marie-Gabrielle|||0000-0001-7408-7792 Knol, Maria J.|||0000-0002-3597-1531 Le Grand, Quentin|||0000-0002-9299-0747 Evans, Tavia E.|||0000-0003-2390-286X Mishra, Aniket|||0000-0002-8141-1543 Tsuchida, Ami|||0000-0001-5160-6203 Roshchupkin, Gennady V.|||0000-0002-3403-2313 Konuma, Takahiro Trégouët, David-Alexandre|||0000-0001-9084-7800 Romero, Jose Rafael|||0000-0002-1101-2950 Frenzel, Stefan|||0000-0001-5087-5970 Luciano, Michelle|||0000-0002-7306-3008 Hofer, Edith Bourgey, Mathieu|||0000-0002-8432-834X Dueker, Nicole D. Delgado Martínez, María Pilar|||0000-0002-1628-4488 Hilal, Saima Tankard, Rick M.|||0000-0002-8847-9401 Dubost, Florian Shin, Jean|||0000-0001-7353-5178 Saba, Yasaman|||0000-0002-3549-2493 Armstrong, Nicola|||0000-0002-4477-293X Bordes, Constance|||0000-0003-3367-1778 Bastin, Mark E. Beiser, Alexa Brodaty, Henry|||0000-0001-9487-6617 Bülow, Robin|||0000-0003-1884-5784 Carrera, Caty|||0000-0002-0804-0969 Chen, Christopher Cheng, Ching-Yu|||0000-0003-0655-885X Deary, Ian J.|||0000-0002-1733-263X Gampawar, Piyush G. Himali, Jayandra J.|||0000-0003-1391-9481 Jiang, Jiyang|||0000-0002-2147-6302 Kawaguchi, Takahisa Li, Shuo|||0000-0003-2331-2448 Macalli, Melissa|||0000-0003-3008-8720 Marquis, Pascale Morris, Zoe Muñoz Maniega, Susana|||0000-0001-5185-6384 Miyamoto, Susumu Okawa, Masakazu|||0000-0002-5414-1293 Paradise, Matthew Parva, Pedram Rundek, Tatjana|||0000-0002-7115-9815 Sargurupremraj, Muralidharan|||0000-0003-1684-3750 Schilling, Sabrina Setoh, Kazuya Soukarieh, Omar Tabara, Yasuharu Teumer, Alexander|||0000-0002-8309-094X Thalamuthu, Anbupalam|||0000-0002-7114-1260 Trollor, Julian|||0000-0002-7685-2977 Valdés Hernández, Maria C. Vernooij, Meike W. Völker, Uwe|||0000-0002-5689-3448 Wittfeld, Katharina|||0000-0003-4383-5043 Wong, Tien Yin|||0000-0002-8448-1264 Wright, Margaret J.|||0000-0001-7133-4970 Zhang, Junyi Zhao, Wanting Zhu, Yi-Cheng Schmidt, Helena|||0000-0001-9773-9992 Sachdev, Perminder S.|||0000-0002-9595-3220 Wen, Wei|||0000-0003-2753-3870 Yoshida, Kazumichi Joutel, Anne Satizabal, Claudia L.|||0000-0002-1115-4430 Sacco, Ralph L. Bourque, Guillaume|||0000-0002-3933-9656 Lathrop, Mark Paus, Tomas|||0000-0003-1495-9338 Fernández Cadenas, Israel|||0000-0003-4821-2363 Yang, Qiong|||0000-0002-3658-1375 Mazoyer, Bernard|||0000-0003-0970-2837 Boutinaud, Philippe Okada, Yukinori|||0000-0002-0311-8472 Grabe, Hans J.|||0000-0003-3684-4208 Mather, Karen A.|||0000-0003-4143-8941 Schmidt, Reinhold Joliot, Marc|||0000-0001-7792-308X Ikram, M. Arfan|||0000-0003-0372-8585 Matsuda, Fumihiko Tzourio, Christophe|||0000-0002-6517-2984 Wardlaw, Joanna|||0000-0002-9812-6642 Seshadri, Sudha|||0000-0001-6135-2622 Adams, Hieab H. H.|||0000-0003-3687-2508 Debette, Stéphanie|||0000-0001-8675-7968 |
| author |
Duperron, Marie-Gabrielle|||0000-0001-7408-7792 |
| author_facet |
Duperron, Marie-Gabrielle|||0000-0001-7408-7792 Knol, Maria J.|||0000-0002-3597-1531 Le Grand, Quentin|||0000-0002-9299-0747 Evans, Tavia E.|||0000-0003-2390-286X Mishra, Aniket|||0000-0002-8141-1543 Tsuchida, Ami|||0000-0001-5160-6203 Roshchupkin, Gennady V.|||0000-0002-3403-2313 Konuma, Takahiro Trégouët, David-Alexandre|||0000-0001-9084-7800 Romero, Jose Rafael|||0000-0002-1101-2950 Frenzel, Stefan|||0000-0001-5087-5970 Luciano, Michelle|||0000-0002-7306-3008 Hofer, Edith Bourgey, Mathieu|||0000-0002-8432-834X Dueker, Nicole D. Delgado Martínez, María Pilar|||0000-0002-1628-4488 Hilal, Saima Tankard, Rick M.|||0000-0002-8847-9401 Dubost, Florian Shin, Jean|||0000-0001-7353-5178 Saba, Yasaman|||0000-0002-3549-2493 Armstrong, Nicola|||0000-0002-4477-293X Bordes, Constance|||0000-0003-3367-1778 Bastin, Mark E. Beiser, Alexa Brodaty, Henry|||0000-0001-9487-6617 Bülow, Robin|||0000-0003-1884-5784 Carrera, Caty|||0000-0002-0804-0969 Chen, Christopher Cheng, Ching-Yu|||0000-0003-0655-885X Deary, Ian J.|||0000-0002-1733-263X Gampawar, Piyush G. Himali, Jayandra J.|||0000-0003-1391-9481 Jiang, Jiyang|||0000-0002-2147-6302 Kawaguchi, Takahisa Li, Shuo|||0000-0003-2331-2448 Macalli, Melissa|||0000-0003-3008-8720 Marquis, Pascale Morris, Zoe Muñoz Maniega, Susana|||0000-0001-5185-6384 Miyamoto, Susumu Okawa, Masakazu|||0000-0002-5414-1293 Paradise, Matthew Parva, Pedram Rundek, Tatjana|||0000-0002-7115-9815 Sargurupremraj, Muralidharan|||0000-0003-1684-3750 Schilling, Sabrina Setoh, Kazuya Soukarieh, Omar Tabara, Yasuharu Teumer, Alexander|||0000-0002-8309-094X Thalamuthu, Anbupalam|||0000-0002-7114-1260 Trollor, Julian|||0000-0002-7685-2977 Valdés Hernández, Maria C. Vernooij, Meike W. Völker, Uwe|||0000-0002-5689-3448 Wittfeld, Katharina|||0000-0003-4383-5043 Wong, Tien Yin|||0000-0002-8448-1264 Wright, Margaret J.|||0000-0001-7133-4970 Zhang, Junyi Zhao, Wanting Zhu, Yi-Cheng Schmidt, Helena|||0000-0001-9773-9992 Sachdev, Perminder S.|||0000-0002-9595-3220 Wen, Wei|||0000-0003-2753-3870 Yoshida, Kazumichi Joutel, Anne Satizabal, Claudia L.|||0000-0002-1115-4430 Sacco, Ralph L. Bourque, Guillaume|||0000-0002-3933-9656 Lathrop, Mark Paus, Tomas|||0000-0003-1495-9338 Fernández Cadenas, Israel|||0000-0003-4821-2363 Yang, Qiong|||0000-0002-3658-1375 Mazoyer, Bernard|||0000-0003-0970-2837 Boutinaud, Philippe Okada, Yukinori|||0000-0002-0311-8472 Grabe, Hans J.|||0000-0003-3684-4208 Mather, Karen A.|||0000-0003-4143-8941 Schmidt, Reinhold Joliot, Marc|||0000-0001-7792-308X Ikram, M. Arfan|||0000-0003-0372-8585 Matsuda, Fumihiko Tzourio, Christophe|||0000-0002-6517-2984 Wardlaw, Joanna|||0000-0002-9812-6642 Seshadri, Sudha|||0000-0001-6135-2622 Adams, Hieab H. H.|||0000-0003-3687-2508 Debette, Stéphanie|||0000-0001-8675-7968 |
| author_role |
author |
| author2 |
Knol, Maria J.|||0000-0002-3597-1531 Le Grand, Quentin|||0000-0002-9299-0747 Evans, Tavia E.|||0000-0003-2390-286X Mishra, Aniket|||0000-0002-8141-1543 Tsuchida, Ami|||0000-0001-5160-6203 Roshchupkin, Gennady V.|||0000-0002-3403-2313 Konuma, Takahiro Trégouët, David-Alexandre|||0000-0001-9084-7800 Romero, Jose Rafael|||0000-0002-1101-2950 Frenzel, Stefan|||0000-0001-5087-5970 Luciano, Michelle|||0000-0002-7306-3008 Hofer, Edith Bourgey, Mathieu|||0000-0002-8432-834X Dueker, Nicole D. Delgado Martínez, María Pilar|||0000-0002-1628-4488 Hilal, Saima Tankard, Rick M.|||0000-0002-8847-9401 Dubost, Florian Shin, Jean|||0000-0001-7353-5178 Saba, Yasaman|||0000-0002-3549-2493 Armstrong, Nicola|||0000-0002-4477-293X Bordes, Constance|||0000-0003-3367-1778 Bastin, Mark E. Beiser, Alexa Brodaty, Henry|||0000-0001-9487-6617 Bülow, Robin|||0000-0003-1884-5784 Carrera, Caty|||0000-0002-0804-0969 Chen, Christopher Cheng, Ching-Yu|||0000-0003-0655-885X Deary, Ian J.|||0000-0002-1733-263X Gampawar, Piyush G. Himali, Jayandra J.|||0000-0003-1391-9481 Jiang, Jiyang|||0000-0002-2147-6302 Kawaguchi, Takahisa Li, Shuo|||0000-0003-2331-2448 Macalli, Melissa|||0000-0003-3008-8720 Marquis, Pascale Morris, Zoe Muñoz Maniega, Susana|||0000-0001-5185-6384 Miyamoto, Susumu Okawa, Masakazu|||0000-0002-5414-1293 Paradise, Matthew Parva, Pedram Rundek, Tatjana|||0000-0002-7115-9815 Sargurupremraj, Muralidharan|||0000-0003-1684-3750 Schilling, Sabrina Setoh, Kazuya Soukarieh, Omar Tabara, Yasuharu Teumer, Alexander|||0000-0002-8309-094X Thalamuthu, Anbupalam|||0000-0002-7114-1260 Trollor, Julian|||0000-0002-7685-2977 Valdés Hernández, Maria C. Vernooij, Meike W. Völker, Uwe|||0000-0002-5689-3448 Wittfeld, Katharina|||0000-0003-4383-5043 Wong, Tien Yin|||0000-0002-8448-1264 Wright, Margaret J.|||0000-0001-7133-4970 Zhang, Junyi Zhao, Wanting Zhu, Yi-Cheng Schmidt, Helena|||0000-0001-9773-9992 Sachdev, Perminder S.|||0000-0002-9595-3220 Wen, Wei|||0000-0003-2753-3870 Yoshida, Kazumichi Joutel, Anne Satizabal, Claudia L.|||0000-0002-1115-4430 Sacco, Ralph L. Bourque, Guillaume|||0000-0002-3933-9656 Lathrop, Mark Paus, Tomas|||0000-0003-1495-9338 Fernández Cadenas, Israel|||0000-0003-4821-2363 Yang, Qiong|||0000-0002-3658-1375 Mazoyer, Bernard|||0000-0003-0970-2837 Boutinaud, Philippe Okada, Yukinori|||0000-0002-0311-8472 Grabe, Hans J.|||0000-0003-3684-4208 Mather, Karen A.|||0000-0003-4143-8941 Schmidt, Reinhold Joliot, Marc|||0000-0001-7792-308X Ikram, M. Arfan|||0000-0003-0372-8585 Matsuda, Fumihiko Tzourio, Christophe|||0000-0002-6517-2984 Wardlaw, Joanna|||0000-0002-9812-6642 Seshadri, Sudha|||0000-0001-6135-2622 Adams, Hieab H. H.|||0000-0003-3687-2508 Debette, Stéphanie|||0000-0001-8675-7968 |
| 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 |
| dc.contributor.none.fl_str_mv |
Universitat Autònoma de Barcelona |
| dc.subject.none.fl_str_mv |
Neurology Stroke Genome-wide association studies |
| topic |
Neurology Stroke Genome-wide association studies |
| description |
Perivascular space (PVS) burden is an emerging, poorly understood, magnetic resonance imaging marker of cerebral small vessel disease, a leading cause of stroke and dementia. Genome-wide association studies in up to 40,095 participants (18 population-based cohorts, 66.3 ± 8.6 yr, 96.9% European ancestry) revealed 24 genome-wide significant PVS risk loci, mainly in the white matter. These were associated with white matter PVS already in young adults (N = 1,748; 22.1 ± 2.3 yr) and were enriched in early-onset leukodystrophy genes and genes expressed in fetal brain endothelial cells, suggesting early-life mechanisms. In total, 53% of white matter PVS risk loci showed nominally significant associations (27% after multiple-testing correction) in a Japanese population-based cohort (N = 2,862; 68.3 ± 5.3 yr). Mendelian randomization supported causal associations of high blood pressure with basal ganglia and hippocampal PVS, and of basal ganglia PVS and hippocampal PVS with stroke, accounting for blood pressure. Our findings provide insight into the biology of PVS and cerebral small vessel disease, pointing to pathways involving extracellular matrix, membrane transport and developmental processes, and the potential for genetically informed prioritization of drug targets. Genomic analyses of large population-based cohorts uncover the genetic determinants of perivascular space burden, an MRI marker of cerebral small vessel disease, across the lifespan, and reveal potential pathways implicated in the etiology of stroke and dementia. |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2 2023-01-01 2023 2023-01-01 |
| 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/280931 https://dx.doi.org/urn:doi:10.1038/s41591-023-02268-w |
| url |
https://ddd.uab.cat/record/280931 https://dx.doi.org/urn:doi:10.1038/s41591-023-02268-w |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI14/01535 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI17/02222 |
| 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 |
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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 |
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reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona |
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Universitat Autònoma de Barcelona |
| reponame_str |
Dipòsit Digital de Documents de la UAB |
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Dipòsit Digital de Documents de la UAB |
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1869418248449032192 |
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Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel diseaseDuperron, Marie-Gabrielle|||0000-0001-7408-7792Knol, Maria J.|||0000-0002-3597-1531Le Grand, Quentin|||0000-0002-9299-0747Evans, Tavia E.|||0000-0003-2390-286XMishra, Aniket|||0000-0002-8141-1543Tsuchida, Ami|||0000-0001-5160-6203Roshchupkin, Gennady V.|||0000-0002-3403-2313Konuma, TakahiroTrégouët, David-Alexandre|||0000-0001-9084-7800Romero, Jose Rafael|||0000-0002-1101-2950Frenzel, Stefan|||0000-0001-5087-5970Luciano, Michelle|||0000-0002-7306-3008Hofer, EdithBourgey, Mathieu|||0000-0002-8432-834XDueker, Nicole D.Delgado Martínez, María Pilar|||0000-0002-1628-4488Hilal, SaimaTankard, Rick M.|||0000-0002-8847-9401Dubost, FlorianShin, Jean|||0000-0001-7353-5178Saba, Yasaman|||0000-0002-3549-2493Armstrong, Nicola|||0000-0002-4477-293XBordes, Constance|||0000-0003-3367-1778Bastin, Mark E.Beiser, AlexaBrodaty, Henry|||0000-0001-9487-6617Bülow, Robin|||0000-0003-1884-5784Carrera, Caty|||0000-0002-0804-0969Chen, ChristopherCheng, Ching-Yu|||0000-0003-0655-885XDeary, Ian J.|||0000-0002-1733-263XGampawar, Piyush G.Himali, Jayandra J.|||0000-0003-1391-9481Jiang, Jiyang|||0000-0002-2147-6302Kawaguchi, TakahisaLi, Shuo|||0000-0003-2331-2448Macalli, Melissa|||0000-0003-3008-8720Marquis, PascaleMorris, ZoeMuñoz Maniega, Susana|||0000-0001-5185-6384Miyamoto, SusumuOkawa, Masakazu|||0000-0002-5414-1293Paradise, MatthewParva, PedramRundek, Tatjana|||0000-0002-7115-9815Sargurupremraj, Muralidharan|||0000-0003-1684-3750Schilling, SabrinaSetoh, KazuyaSoukarieh, OmarTabara, YasuharuTeumer, Alexander|||0000-0002-8309-094XThalamuthu, Anbupalam|||0000-0002-7114-1260Trollor, Julian|||0000-0002-7685-2977Valdés Hernández, Maria C.Vernooij, Meike W.Völker, Uwe|||0000-0002-5689-3448Wittfeld, Katharina|||0000-0003-4383-5043Wong, Tien Yin|||0000-0002-8448-1264Wright, Margaret J.|||0000-0001-7133-4970Zhang, JunyiZhao, WantingZhu, Yi-ChengSchmidt, Helena|||0000-0001-9773-9992Sachdev, Perminder S.|||0000-0002-9595-3220Wen, Wei|||0000-0003-2753-3870Yoshida, KazumichiJoutel, AnneSatizabal, Claudia L.|||0000-0002-1115-4430Sacco, Ralph L.Bourque, Guillaume|||0000-0002-3933-9656Lathrop, MarkPaus, Tomas|||0000-0003-1495-9338Fernández Cadenas, Israel|||0000-0003-4821-2363Yang, Qiong|||0000-0002-3658-1375Mazoyer, Bernard|||0000-0003-0970-2837Boutinaud, PhilippeOkada, Yukinori|||0000-0002-0311-8472Grabe, Hans J.|||0000-0003-3684-4208Mather, Karen A.|||0000-0003-4143-8941Schmidt, ReinholdJoliot, Marc|||0000-0001-7792-308XIkram, M. Arfan|||0000-0003-0372-8585Matsuda, FumihikoTzourio, Christophe|||0000-0002-6517-2984Wardlaw, Joanna|||0000-0002-9812-6642Seshadri, Sudha|||0000-0001-6135-2622Adams, Hieab H. H.|||0000-0003-3687-2508Debette, Stéphanie|||0000-0001-8675-7968NeurologyStrokeGenome-wide association studiesPerivascular space (PVS) burden is an emerging, poorly understood, magnetic resonance imaging marker of cerebral small vessel disease, a leading cause of stroke and dementia. Genome-wide association studies in up to 40,095 participants (18 population-based cohorts, 66.3 ± 8.6 yr, 96.9% European ancestry) revealed 24 genome-wide significant PVS risk loci, mainly in the white matter. These were associated with white matter PVS already in young adults (N = 1,748; 22.1 ± 2.3 yr) and were enriched in early-onset leukodystrophy genes and genes expressed in fetal brain endothelial cells, suggesting early-life mechanisms. In total, 53% of white matter PVS risk loci showed nominally significant associations (27% after multiple-testing correction) in a Japanese population-based cohort (N = 2,862; 68.3 ± 5.3 yr). Mendelian randomization supported causal associations of high blood pressure with basal ganglia and hippocampal PVS, and of basal ganglia PVS and hippocampal PVS with stroke, accounting for blood pressure. Our findings provide insight into the biology of PVS and cerebral small vessel disease, pointing to pathways involving extracellular matrix, membrane transport and developmental processes, and the potential for genetically informed prioritization of drug targets. Genomic analyses of large population-based cohorts uncover the genetic determinants of perivascular space burden, an MRI marker of cerebral small vessel disease, across the lifespan, and reveal potential pathways implicated in the etiology of stroke and dementia.Universitat Autònoma de Barcelona 22023-01-0120232023-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/280931https://dx.doi.org/urn:doi:10.1038/s41591-023-02268-wreponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI14/01535Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI17/02222open 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:2809312026-06-06T12:50:31Z |
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15,300719 |