Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease.
Alzheimer disease (AD), Frontotemporal lobar degeneration (FTD), Amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD) have a certain degree of clinical, pathological and molecular overlap. Previous studies indicate that causative mutations in AD and FTD/ALS genes can be found in clinical f...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-11-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC5683650?pdf=render |
| _version_ | 1811289498127958016 |
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| author | Maria Victoria Fernández Jong Hun Kim John P Budde Kathleen Black Alexandra Medvedeva Ben Saef Yuetiva Deming Jorge Del-Aguila Laura Ibañez Umber Dube Oscar Harari Joanne Norton Rachel Chasse John C Morris Alison Goate NIA-LOAD family study group NCRAD Carlos Cruchaga |
| author_facet | Maria Victoria Fernández Jong Hun Kim John P Budde Kathleen Black Alexandra Medvedeva Ben Saef Yuetiva Deming Jorge Del-Aguila Laura Ibañez Umber Dube Oscar Harari Joanne Norton Rachel Chasse John C Morris Alison Goate NIA-LOAD family study group NCRAD Carlos Cruchaga |
| author_sort | Maria Victoria Fernández |
| collection | DOAJ |
| description | Alzheimer disease (AD), Frontotemporal lobar degeneration (FTD), Amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD) have a certain degree of clinical, pathological and molecular overlap. Previous studies indicate that causative mutations in AD and FTD/ALS genes can be found in clinical familial AD. We examined the presence of causative and low frequency coding variants in the AD, FTD, ALS and PD Mendelian genes, in over 450 families with clinical history of AD and over 11,710 sporadic cases and cognitive normal participants from North America. Known pathogenic mutations were found in 1.05% of the sporadic cases, in 0.69% of the cognitively normal participants and in 4.22% of the families. A trend towards enrichment, albeit non-significant, was observed for most AD, FTD and PD genes. Only PSEN1 and PINK1 showed consistent association with AD cases when we used ExAC as the control population. These results suggest that current study designs may contain heterogeneity and contamination of the control population, and that current statistical methods for the discovery of novel genes with real pathogenic variants in complex late onset diseases may be inadequate or underpowered to identify genes carrying pathogenic mutations. |
| first_indexed | 2024-04-13T03:55:52Z |
| format | Article |
| id | doaj.art-c24c203611fa48d2b14d18c2f9324a8e |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-04-13T03:55:52Z |
| publishDate | 2017-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-c24c203611fa48d2b14d18c2f9324a8e2022-12-22T03:03:39ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042017-11-011311e100704510.1371/journal.pgen.1007045Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease.Maria Victoria FernándezJong Hun KimJohn P BuddeKathleen BlackAlexandra MedvedevaBen SaefYuetiva DemingJorge Del-AguilaLaura IbañezUmber DubeOscar HarariJoanne NortonRachel ChasseJohn C MorrisAlison GoateNIA-LOAD family study groupNCRADCarlos CruchagaAlzheimer disease (AD), Frontotemporal lobar degeneration (FTD), Amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD) have a certain degree of clinical, pathological and molecular overlap. Previous studies indicate that causative mutations in AD and FTD/ALS genes can be found in clinical familial AD. We examined the presence of causative and low frequency coding variants in the AD, FTD, ALS and PD Mendelian genes, in over 450 families with clinical history of AD and over 11,710 sporadic cases and cognitive normal participants from North America. Known pathogenic mutations were found in 1.05% of the sporadic cases, in 0.69% of the cognitively normal participants and in 4.22% of the families. A trend towards enrichment, albeit non-significant, was observed for most AD, FTD and PD genes. Only PSEN1 and PINK1 showed consistent association with AD cases when we used ExAC as the control population. These results suggest that current study designs may contain heterogeneity and contamination of the control population, and that current statistical methods for the discovery of novel genes with real pathogenic variants in complex late onset diseases may be inadequate or underpowered to identify genes carrying pathogenic mutations.http://europepmc.org/articles/PMC5683650?pdf=render |
| spellingShingle | Maria Victoria Fernández Jong Hun Kim John P Budde Kathleen Black Alexandra Medvedeva Ben Saef Yuetiva Deming Jorge Del-Aguila Laura Ibañez Umber Dube Oscar Harari Joanne Norton Rachel Chasse John C Morris Alison Goate NIA-LOAD family study group NCRAD Carlos Cruchaga Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease. PLoS Genetics |
| title | Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease. |
| title_full | Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease. |
| title_fullStr | Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease. |
| title_full_unstemmed | Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease. |
| title_short | Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease. |
| title_sort | analysis of neurodegenerative mendelian genes in clinically diagnosed alzheimer disease |
| url | http://europepmc.org/articles/PMC5683650?pdf=render |
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