Whole Exome Sequencing in 20,197 Persons for Rare Variants in Alzheimer Disease

Abstract

1

Association of Rare Coding Mutations With Alzheimer Disease and Other Dementias Among Adults of European Ancestry

“…Our study also suggests that participants with AD have a significantly higher burden of deleterious rare coding variants in known AD, AD-related, or other dementia genes compared with controls. This observation generalizes previous findings in SORL1, 31,34,35 MAPT, 32,36 TREM2, 4,37,38 and ABCA7 33,39-41 that both common and rare variants in the same gene may independently contribute to AD risk.…”

Association of Rare Coding Mutations With Alzheimer Disease and Other Dementias Among Adults of European Ancestry

“…Our study also suggests that participants with AD have a significantly higher burden of deleterious rare coding variants in known AD, AD-related, or other dementia genes compared with controls. This observation generalizes previous findings in SORL1, 31,34,35 MAPT, 32,36 TREM2, 4,37,38 and ABCA7 33,39-41 that both common and rare variants in the same gene may independently contribute to AD risk.…”

Genetic Analyses of Alzheimer’s Disease in China: Achievements and Perspectives

“…The ADSP was the largest whole-exome sequencing project in AD research so far. 35 It highlighted rare coding variants in the SORL1 gene identified by previous GWAS 48 and identified several novel genes (IGHG3, STAG3, and AC099552.4) harboring functional variants. 35 In total, around 10 genes with rare functional variants were identified by NGS studies so far, providing promising targets for further mechanism studies and therapeutic treatments.…”

A Machine Learning Method to Identify Genetic Variants Potentially Associated With Alzheimer’s Disease

“…The dataset used in these analyses was generously provided by the Alzheimer’s Disease Sequencing Project (ADSP), and has been previously described in detail in other manuscripts ( Harold et al, 2009 ; Raghavan et al, 2018 ) and online at niagads.org . To summarize, individuals in this dataset were from well-characterized cohorts, including ∼6,000 individuals diagnosed with late-onset Alzheimer’s disease (mean age of diagnosis: 75.4) and ∼5,000 elderly controls without dementia (mean age: 86.1, at the date of last visit to AD practitioner).…”

Association of Rare Coding Mutations With Alzheimer Disease and Other Dementias Among Adults of European Ancestry

“…Our study also suggests that participants with AD have a significantly higher burden of deleterious rare coding variants in known AD, AD-related, or other dementia genes compared with controls. This observation generalizes previous findings in SORL1, 31,34,35 MAPT, 32,36 TREM2, 4,37,38 and ABCA7 33,39-41 that both common and rare variants in the same gene may independently contribute to AD risk.…”

Genetic Analyses of Alzheimer’s Disease in China: Achievements and Perspectives

“…The ADSP was the largest whole-exome sequencing project in AD research so far. 35 It highlighted rare coding variants in the SORL1 gene identified by previous GWAS 48 and identified several novel genes (IGHG3, STAG3, and AC099552.4) harboring functional variants. 35 In total, around 10 genes with rare functional variants were identified by NGS studies so far, providing promising targets for further mechanism studies and therapeutic treatments.…”

A Machine Learning Method to Identify Genetic Variants Potentially Associated With Alzheimer’s Disease

“…The dataset used in these analyses was generously provided by the Alzheimer’s Disease Sequencing Project (ADSP), and has been previously described in detail in other manuscripts ( Harold et al, 2009 ; Raghavan et al, 2018 ) and online at niagads.org . To summarize, individuals in this dataset were from well-characterized cohorts, including ∼6,000 individuals diagnosed with late-onset Alzheimer’s disease (mean age of diagnosis: 75.4) and ∼5,000 elderly controls without dementia (mean age: 86.1, at the date of last visit to AD practitioner).…”

Association of Rare Coding Mutations With Alzheimer Disease and Other Dementias Among Adults of European Ancestry

“…Our study also suggests that participants with AD have a significantly higher burden of deleterious rare coding variants in known AD, AD-related, or other dementia genes compared with controls. This observation generalizes previous findings in SORL1, 31,34,35 MAPT, 32,36 TREM2, 4,37,38 and ABCA7 33,39-41 that both common and rare variants in the same gene may independently contribute to AD risk.…”

Genetic Analyses of Alzheimer’s Disease in China: Achievements and Perspectives

“…The ADSP was the largest whole-exome sequencing project in AD research so far. 35 It highlighted rare coding variants in the SORL1 gene identified by previous GWAS 48 and identified several novel genes (IGHG3, STAG3, and AC099552.4) harboring functional variants. 35 In total, around 10 genes with rare functional variants were identified by NGS studies so far, providing promising targets for further mechanism studies and therapeutic treatments.…”

A Machine Learning Method to Identify Genetic Variants Potentially Associated With Alzheimer’s Disease

“…The dataset used in these analyses was generously provided by the Alzheimer’s Disease Sequencing Project (ADSP), and has been previously described in detail in other manuscripts ( Harold et al, 2009 ; Raghavan et al, 2018 ) and online at niagads.org . To summarize, individuals in this dataset were from well-characterized cohorts, including ∼6,000 individuals diagnosed with late-onset Alzheimer’s disease (mean age of diagnosis: 75.4) and ∼5,000 elderly controls without dementia (mean age: 86.1, at the date of last visit to AD practitioner).…”