A Mutation in DAOA Modifies the Age of Onset in PSEN1 E280A Alzheimer's Disease
We previously reported age of onset (AOO) modifier genes in the world’s largest pedigree segregating early-onset Alzheimer’s disease (AD), caused by the p.Glu280Ala (E280A) mutation in the PSEN1 gene. Here we report the results of a targeted analysis of functional exonic variants in those AOO modifi...
- Autores:
- Tipo de recurso:
- Fecha de publicación:
- 2016
- Institución:
- Universidad del Rosario
- Repositorio:
- Repositorio EdocUR - U. Rosario
- Idioma:
- eng
- OAI Identifier:
- oai:repository.urosario.edu.co:10336/27575
- Acceso en línea:
- https://doi.org/10.1155/2016/9760314
https://repository.urosario.edu.co/handle/10336/27575
- Palabra clave:
- A Mutation
DAOA Modifies
Age of Onset
PSEN1 E280A
Alzheimer’s Disease
- Rights
- License
- Abierto (Texto Completo)
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38ea231b-5d48-4eef-b877-87eca4f5f3ff-1b2b5ed0d-6773-46bb-acd3-c50d9dc9460d-1bff3f370-68f0-4f53-bad1-dbca3ebb9dab-1e6d102c0-724a-44f0-8e5d-1a234fc5fe71-10b1e05b6-84b5-4b22-a9cb-1c4f01d55b63-1d2d59976-8845-4050-96b5-82cfd24dc543-1506bf07a-c897-45d7-b881-a12985bbfea6-19b1690cb-266c-4842-a28f-a8ed00d4390d-13e34a620-2f12-496e-bf1d-feabacbf1fe2-110548610-12020-08-19T14:42:48Z2020-08-19T14:42:48Z2016-01-05We previously reported age of onset (AOO) modifier genes in the world’s largest pedigree segregating early-onset Alzheimer’s disease (AD), caused by the p.Glu280Ala (E280A) mutation in the PSEN1 gene. Here we report the results of a targeted analysis of functional exonic variants in those AOO modifier genes in sixty individuals with PSEN1 E280A AD who were whole-exome genotyped for ~250,000 variants. Standard quality control, filtering, and annotation for functional variants were applied, and common functional variants located in those previously reported as AOO modifier loci were selected. Multiloci linear mixed-effects models were used to test the association between these variants and AOO. An exonic missense mutation in the G72 (DAOA) gene (rs2391191, P = 1.94 × 10?4, PFDR = 9.34 × 10?3) was found to modify AOO in PSEN1 E280A AD. Nominal associations of missense mutations in the CLUAP1 (rs9790, P = 7.63 × 10?3, PFDR = 0.1832) and EXOC2 (rs17136239, P = 0.0325, PFDR = 0.391) genes were also found. Previous studies have linked polymorphisms in the DAOA gene with the occurrence of neuropsychiatric symptoms such as depression, apathy, aggression, delusions, hallucinations, and psychosis in AD. Our findings strongly suggest that this new conspicuous functional AOO modifier within the G72 (DAOA) gene could be pivotal for understanding the genetic basis of ADapplication/pdfhttps://doi.org/10.1155/2016/9760314ISSN: 2090-5904EISSN: 1687-5443https://repository.urosario.edu.co/handle/10336/27575engHindawiNeural Plasticity; Special Issue Neural Plasticity in Obesity and Psychiatric DisordersVol. 2016Neural Plasticity; Special Issue Neural Plasticity in Obesity and Psychiatric Disorders, ISSN: 2090-5904; EISSN: 1687-5443 , Vol.2016, Article ID 9760314 (December, 2015); 7 pp. https://www.hindawi.com/journals/np/2016/9760314/Abierto (Texto Completo)http://purl.org/coar/access_right/c_abf2Neural Plasticity; Special Issue Neural Plasticity in Obesity and Psychiatric Disordersinstname:Universidad del Rosarioreponame:Repositorio Institucional EdocURA MutationDAOA ModifiesAge of OnsetPSEN1 E280AAlzheimer’s DiseaseA Mutation in DAOA Modifies the Age of Onset in PSEN1 E280A Alzheimer's DiseaseUna mutación en DAOA modifica la edad de inicio en la enfermedad de Alzheimer PSEN1 E280AarticleArtículohttp://purl.org/coar/version/c_970fb48d4fbd8a85http://purl.org/coar/resource_type/c_6501Vélez, Jorge I.Rivera, DoraMastronardi, Claudio A.Patel, Hardip R.Tobón, CarlosVillegas, AndrésCai, YepingEasteal, SimonLopera, FranciscoArcos-Burgos, MauricioORIGINAL9760314.pdfapplication/pdf1366864https://repository.urosario.edu.co/bitstreams/5c69bf5f-5f41-4a8e-b71d-76b59110457f/download3dd98883e258527931fe53c1f209d1baMD51TEXT9760314.pdf.txt9760314.pdf.txtExtracted texttext/plain38278https://repository.urosario.edu.co/bitstreams/02995d29-2e16-4e17-891a-ccdab483a529/download372e2b215ed3ca7eb4216b8151737c19MD52THUMBNAIL9760314.pdf.jpg9760314.pdf.jpgGenerated Thumbnailimage/jpeg4304https://repository.urosario.edu.co/bitstreams/03d79ec5-d71d-4572-8b77-5bec6734aa73/download651e3ae97e0715b69e023dcc0920c7b5MD5310336/27575oai:repository.urosario.edu.co:10336/275752021-06-03 00:50:15.492https://repository.urosario.edu.coRepositorio institucional EdocURedocur@urosario.edu.co |
dc.title.spa.fl_str_mv |
A Mutation in DAOA Modifies the Age of Onset in PSEN1 E280A Alzheimer's Disease |
dc.title.TranslatedTitle.spa.fl_str_mv |
Una mutación en DAOA modifica la edad de inicio en la enfermedad de Alzheimer PSEN1 E280A |
title |
A Mutation in DAOA Modifies the Age of Onset in PSEN1 E280A Alzheimer's Disease |
spellingShingle |
A Mutation in DAOA Modifies the Age of Onset in PSEN1 E280A Alzheimer's Disease A Mutation DAOA Modifies Age of Onset PSEN1 E280A Alzheimer’s Disease |
title_short |
A Mutation in DAOA Modifies the Age of Onset in PSEN1 E280A Alzheimer's Disease |
title_full |
A Mutation in DAOA Modifies the Age of Onset in PSEN1 E280A Alzheimer's Disease |
title_fullStr |
A Mutation in DAOA Modifies the Age of Onset in PSEN1 E280A Alzheimer's Disease |
title_full_unstemmed |
A Mutation in DAOA Modifies the Age of Onset in PSEN1 E280A Alzheimer's Disease |
title_sort |
A Mutation in DAOA Modifies the Age of Onset in PSEN1 E280A Alzheimer's Disease |
dc.subject.keyword.spa.fl_str_mv |
A Mutation DAOA Modifies Age of Onset PSEN1 E280A Alzheimer’s Disease |
topic |
A Mutation DAOA Modifies Age of Onset PSEN1 E280A Alzheimer’s Disease |
description |
We previously reported age of onset (AOO) modifier genes in the world’s largest pedigree segregating early-onset Alzheimer’s disease (AD), caused by the p.Glu280Ala (E280A) mutation in the PSEN1 gene. Here we report the results of a targeted analysis of functional exonic variants in those AOO modifier genes in sixty individuals with PSEN1 E280A AD who were whole-exome genotyped for ~250,000 variants. Standard quality control, filtering, and annotation for functional variants were applied, and common functional variants located in those previously reported as AOO modifier loci were selected. Multiloci linear mixed-effects models were used to test the association between these variants and AOO. An exonic missense mutation in the G72 (DAOA) gene (rs2391191, P = 1.94 × 10?4, PFDR = 9.34 × 10?3) was found to modify AOO in PSEN1 E280A AD. Nominal associations of missense mutations in the CLUAP1 (rs9790, P = 7.63 × 10?3, PFDR = 0.1832) and EXOC2 (rs17136239, P = 0.0325, PFDR = 0.391) genes were also found. Previous studies have linked polymorphisms in the DAOA gene with the occurrence of neuropsychiatric symptoms such as depression, apathy, aggression, delusions, hallucinations, and psychosis in AD. Our findings strongly suggest that this new conspicuous functional AOO modifier within the G72 (DAOA) gene could be pivotal for understanding the genetic basis of AD |
publishDate |
2016 |
dc.date.created.spa.fl_str_mv |
2016-01-05 |
dc.date.accessioned.none.fl_str_mv |
2020-08-19T14:42:48Z |
dc.date.available.none.fl_str_mv |
2020-08-19T14:42:48Z |
dc.type.eng.fl_str_mv |
article |
dc.type.coarversion.fl_str_mv |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
dc.type.coar.fl_str_mv |
http://purl.org/coar/resource_type/c_6501 |
dc.type.spa.spa.fl_str_mv |
Artículo |
dc.identifier.doi.none.fl_str_mv |
https://doi.org/10.1155/2016/9760314 |
dc.identifier.issn.none.fl_str_mv |
ISSN: 2090-5904 EISSN: 1687-5443 |
dc.identifier.uri.none.fl_str_mv |
https://repository.urosario.edu.co/handle/10336/27575 |
url |
https://doi.org/10.1155/2016/9760314 https://repository.urosario.edu.co/handle/10336/27575 |
identifier_str_mv |
ISSN: 2090-5904 EISSN: 1687-5443 |
dc.language.iso.spa.fl_str_mv |
eng |
language |
eng |
dc.relation.citationTitle.none.fl_str_mv |
Neural Plasticity; Special Issue Neural Plasticity in Obesity and Psychiatric Disorders |
dc.relation.citationVolume.none.fl_str_mv |
Vol. 2016 |
dc.relation.ispartof.spa.fl_str_mv |
Neural Plasticity; Special Issue Neural Plasticity in Obesity and Psychiatric Disorders, ISSN: 2090-5904; EISSN: 1687-5443 , Vol.2016, Article ID 9760314 (December, 2015); 7 pp. |
dc.relation.uri.spa.fl_str_mv |
https://www.hindawi.com/journals/np/2016/9760314/ |
dc.rights.coar.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
dc.rights.acceso.spa.fl_str_mv |
Abierto (Texto Completo) |
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Abierto (Texto Completo) http://purl.org/coar/access_right/c_abf2 |
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Hindawi |
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Universidad del Rosario |
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