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...

Full description

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)
id EDOCUR2_2afde34a2e95c2d9ea79a43d956ef540
oai_identifier_str oai:repository.urosario.edu.co:10336/27575
network_acronym_str EDOCUR2
network_name_str Repositorio EdocUR - U. Rosario
repository_id_str
spelling 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)
rights_invalid_str_mv Abierto (Texto Completo)
http://purl.org/coar/access_right/c_abf2
dc.format.mimetype.none.fl_str_mv application/pdf
dc.publisher.spa.fl_str_mv Hindawi
dc.source.spa.fl_str_mv Neural Plasticity; Special Issue Neural Plasticity in Obesity and Psychiatric Disorders
institution Universidad del Rosario
dc.source.instname.none.fl_str_mv instname:Universidad del Rosario
dc.source.reponame.none.fl_str_mv reponame:Repositorio Institucional EdocUR
bitstream.url.fl_str_mv https://repository.urosario.edu.co/bitstreams/5c69bf5f-5f41-4a8e-b71d-76b59110457f/download
https://repository.urosario.edu.co/bitstreams/02995d29-2e16-4e17-891a-ccdab483a529/download
https://repository.urosario.edu.co/bitstreams/03d79ec5-d71d-4572-8b77-5bec6734aa73/download
bitstream.checksum.fl_str_mv 3dd98883e258527931fe53c1f209d1ba
372e2b215ed3ca7eb4216b8151737c19
651e3ae97e0715b69e023dcc0920c7b5
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
repository.name.fl_str_mv Repositorio institucional EdocUR
repository.mail.fl_str_mv edocur@urosario.edu.co
_version_ 1814167730834636800