Rare nonsynonymous variants in SORT1 are associated with increased risk for frontotemporal dementia
| Autor(a) principal: | |
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| Data de Publicação: | 2018 |
| Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10451/50450 |
Resumo: | © 2018 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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Rare nonsynonymous variants in SORT1 are associated with increased risk for frontotemporal dementiaFrontotemporal dementiaGenetic associationGranulinRare variantsSortilin© 2018 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)We investigated the genetic role of sortilin (SORT1) in frontotemporal dementia (FTD). SORT1 is the neuronal receptor for granulin, encoded by the progranulin gene (GRN), a major causal gene for inherited FTD. In Belgian cohorts of 636 FTD patients and 1066 unaffected control individuals, we identified 5 patient-only nonsynonymous rare variants in SORT1. Rare variant burden analysis showed a significant increase in rare coding variants in patients compared to control individuals (p = 0.04), particularly in the β-propeller domain (p = 0.04), with 2 rare variants located in the predicted binding site for GRN (p = 0.001). We extended these observations by analyzing 3 independent patient/control cohorts sampled in Spain, Italy, and Portugal by partners of the European Early-Onset Dementia Consortium, together with 1155 FTD patients and 1161 control persons. An additional 7 patient-only nonsynonymous variants were observed in SORT1 in European patients. Meta-analysis of the rare nonsynonymous variants in the Belgian and European patient/control cohorts revealed a significant enrichment in FTD patients (p = 0.006), establishing SORT1 as a genetic risk factor for FTD.The research was funded in part by the Belgian Science Policy Office Interuniversity Attraction Poles program; the Flemish government initiated Methusalem excellence program and Impulse Program on Networks for Dementia Research; the Research Foundation Flanders (FWO), the Agency for Innovation by Science and Technology Flanders (IWT) and the University of Antwerp Research Fund; Belgium. SP received a PhD fellowship of the FWO and EW of the IWT. RG, LB, and GB (IRCCS Fatebenefratelli, Brescia, Italy) were supported by Ricerca Corrente, Italian Ministry of Health.ElsevierRepositório da Universidade de LisboaPhiltjens, StéphanieVan Mossevelde, Saravan der Zee, JulieWauters, ElineDillen, LubinaVandenbulcke, MathieuVandenberghe, RikIvanoiu, AdrianSieben, AnneWillems, ChristianaBenussi, LuisaGhidoni, RobertaBinetti, GiulianoBorroni, BarbaraPadovani, AlessandroPastor, PauDiez-Fairen, MonicaAguilar, MiquelDe Mendonça, AlexandreMiltenberger-Miltenyi, GabrielHernández, IsabelBoada, MerceRuiz, AgustínNacmias, BenedettaSorbi, SandroAlmeida, Maria RosárioSantana, IsabelClarimón, JordiLleó, AlbertoFrisoni, Giovanni B.Sanchez-Valle, RaquelLladó, AlbertGómez-Tortosa, EstrellaGelpi, EllenVan den Broeck, MarleenPeeters, KarinCras, PatrickDe Deyn, Peter P.Engelborghs, SebastiaanCruts, MarcVan Broeckhoven, Christine2021-12-17T16:28:00Z20182018-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/50450engNeurobiol Aging. 2018 Jun;66:181.e3-181.e100197-458010.1016/j.neurobiolaging.2018.02.0111558-1497info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:54:37Zoai:repositorio.ul.pt:10451/50450Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:01:54.013707Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Rare nonsynonymous variants in SORT1 are associated with increased risk for frontotemporal dementia |
| title |
Rare nonsynonymous variants in SORT1 are associated with increased risk for frontotemporal dementia |
| spellingShingle |
Rare nonsynonymous variants in SORT1 are associated with increased risk for frontotemporal dementia Philtjens, Stéphanie Frontotemporal dementia Genetic association Granulin Rare variants Sortilin |
| title_short |
Rare nonsynonymous variants in SORT1 are associated with increased risk for frontotemporal dementia |
| title_full |
Rare nonsynonymous variants in SORT1 are associated with increased risk for frontotemporal dementia |
| title_fullStr |
Rare nonsynonymous variants in SORT1 are associated with increased risk for frontotemporal dementia |
| title_full_unstemmed |
Rare nonsynonymous variants in SORT1 are associated with increased risk for frontotemporal dementia |
| title_sort |
Rare nonsynonymous variants in SORT1 are associated with increased risk for frontotemporal dementia |
| author |
Philtjens, Stéphanie |
| author_facet |
Philtjens, Stéphanie Van Mossevelde, Sara van der Zee, Julie Wauters, Eline Dillen, Lubina Vandenbulcke, Mathieu Vandenberghe, Rik Ivanoiu, Adrian Sieben, Anne Willems, Christiana Benussi, Luisa Ghidoni, Roberta Binetti, Giuliano Borroni, Barbara Padovani, Alessandro Pastor, Pau Diez-Fairen, Monica Aguilar, Miquel De Mendonça, Alexandre Miltenberger-Miltenyi, Gabriel Hernández, Isabel Boada, Merce Ruiz, Agustín Nacmias, Benedetta Sorbi, Sandro Almeida, Maria Rosário Santana, Isabel Clarimón, Jordi Lleó, Alberto Frisoni, Giovanni B. Sanchez-Valle, Raquel Lladó, Albert Gómez-Tortosa, Estrella Gelpi, Ellen Van den Broeck, Marleen Peeters, Karin Cras, Patrick De Deyn, Peter P. Engelborghs, Sebastiaan Cruts, Marc Van Broeckhoven, Christine |
| author_role |
author |
| author2 |
Van Mossevelde, Sara van der Zee, Julie Wauters, Eline Dillen, Lubina Vandenbulcke, Mathieu Vandenberghe, Rik Ivanoiu, Adrian Sieben, Anne Willems, Christiana Benussi, Luisa Ghidoni, Roberta Binetti, Giuliano Borroni, Barbara Padovani, Alessandro Pastor, Pau Diez-Fairen, Monica Aguilar, Miquel De Mendonça, Alexandre Miltenberger-Miltenyi, Gabriel Hernández, Isabel Boada, Merce Ruiz, Agustín Nacmias, Benedetta Sorbi, Sandro Almeida, Maria Rosário Santana, Isabel Clarimón, Jordi Lleó, Alberto Frisoni, Giovanni B. Sanchez-Valle, Raquel Lladó, Albert Gómez-Tortosa, Estrella Gelpi, Ellen Van den Broeck, Marleen Peeters, Karin Cras, Patrick De Deyn, Peter P. Engelborghs, Sebastiaan Cruts, Marc Van Broeckhoven, Christine |
| 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 |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Philtjens, Stéphanie Van Mossevelde, Sara van der Zee, Julie Wauters, Eline Dillen, Lubina Vandenbulcke, Mathieu Vandenberghe, Rik Ivanoiu, Adrian Sieben, Anne Willems, Christiana Benussi, Luisa Ghidoni, Roberta Binetti, Giuliano Borroni, Barbara Padovani, Alessandro Pastor, Pau Diez-Fairen, Monica Aguilar, Miquel De Mendonça, Alexandre Miltenberger-Miltenyi, Gabriel Hernández, Isabel Boada, Merce Ruiz, Agustín Nacmias, Benedetta Sorbi, Sandro Almeida, Maria Rosário Santana, Isabel Clarimón, Jordi Lleó, Alberto Frisoni, Giovanni B. Sanchez-Valle, Raquel Lladó, Albert Gómez-Tortosa, Estrella Gelpi, Ellen Van den Broeck, Marleen Peeters, Karin Cras, Patrick De Deyn, Peter P. Engelborghs, Sebastiaan Cruts, Marc Van Broeckhoven, Christine |
| dc.subject.por.fl_str_mv |
Frontotemporal dementia Genetic association Granulin Rare variants Sortilin |
| topic |
Frontotemporal dementia Genetic association Granulin Rare variants Sortilin |
| description |
© 2018 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
| publishDate |
2018 |
| dc.date.none.fl_str_mv |
2018 2018-01-01T00:00:00Z 2021-12-17T16:28:00Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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http://hdl.handle.net/10451/50450 |
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http://hdl.handle.net/10451/50450 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Neurobiol Aging. 2018 Jun;66:181.e3-181.e10 0197-4580 10.1016/j.neurobiolaging.2018.02.011 1558-1497 |
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openAccess |
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Elsevier |
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Elsevier |
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