Comprehensive Screening for Disease Risk Variants in Early-Onset Alzheimer's Disease Genes in African Americans Identifies Novel PSEN Variants

Aurelie N'Songo; Minerva M. Carrasquillo; Xue Wang; Thuy Nguyen; Yan Asmann; Steven G. Younkin; Mariet Allen; Ranjan Duara; Maria T.Greig Custo; Neill Graff-Radford; Nilüfer Ertekin-Taner

doi:10.3233/JAD-161185

Comprehensive Screening for Disease Risk Variants in Early-Onset Alzheimer's Disease Genes in African Americans Identifies Novel PSEN Variants

Aurelie N'Songo, Minerva M. Carrasquillo, Xue Wang, Thuy Nguyen, Yan Asmann, Steven G. Younkin, Mariet Allen, Ranjan Duara, Maria T.Greig Custo, Neill Graff-Radford, Nilüfer Ertekin-Taner

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

We conducted a comprehensive screening of rare coding variants in an African American cohort to identify novel pathogenic mutations within the early-onset Alzheimer's disease (EOAD) genes (APP, PSEN1, and PSEN2) in this understudied population. Whole-exome sequencing of 238 African American subjects identified 6 rare missense variants within the EOAD genes, which were observed in AD cases but never among controls. These variants were analyzed in an independent cohort of 300 African American subjects in which PSEN2:NM-000447:exon5:c.T331C:p.Phe111Leu and PSEN1-minilin rs777923890 variants were again not observed, indicating that these novel rare variants, may contribute to AD risk in this population.

Original language	English (US)
Pages (from-to)	1215-1222
Number of pages	8
Journal	Journal of Alzheimer's Disease
Volume	56
Issue number	4
DOIs	https://doi.org/10.3233/JAD-161185
State	Published - 2017

Keywords

African Americans
Alzheimer's disease
Early onset
Genetics
Presenilins
Whole exome sequencing

ASJC Scopus subject areas

General Neuroscience
Clinical Psychology
Geriatrics and Gerontology
Psychiatry and Mental health

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10.3233/JAD-161185

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N'Songo, A., Carrasquillo, M. M., Wang, X., Nguyen, T., Asmann, Y., Younkin, S. G., Allen, M., Duara, R., Custo, M. T. G., Graff-Radford, N., & Ertekin-Taner, N. (2017). Comprehensive Screening for Disease Risk Variants in Early-Onset Alzheimer's Disease Genes in African Americans Identifies Novel PSEN Variants. Journal of Alzheimer's Disease, 56(4), 1215-1222. https://doi.org/10.3233/JAD-161185

N'Songo, A, Carrasquillo, MM, Wang, X, Nguyen, T, Asmann, Y , Younkin, SG, Allen, M, Duara, R, Custo, MTG, Graff-Radford, N & Ertekin-Taner, N 2017, 'Comprehensive Screening for Disease Risk Variants in Early-Onset Alzheimer's Disease Genes in African Americans Identifies Novel PSEN Variants', Journal of Alzheimer's Disease, vol. 56, no. 4, pp. 1215-1222. https://doi.org/10.3233/JAD-161185

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title = "Comprehensive Screening for Disease Risk Variants in Early-Onset Alzheimer's Disease Genes in African Americans Identifies Novel PSEN Variants",

abstract = "We conducted a comprehensive screening of rare coding variants in an African American cohort to identify novel pathogenic mutations within the early-onset Alzheimer's disease (EOAD) genes (APP, PSEN1, and PSEN2) in this understudied population. Whole-exome sequencing of 238 African American subjects identified 6 rare missense variants within the EOAD genes, which were observed in AD cases but never among controls. These variants were analyzed in an independent cohort of 300 African American subjects in which PSEN2:NM-000447:exon5:c.T331C:p.Phe111Leu and PSEN1-minilin rs777923890 variants were again not observed, indicating that these novel rare variants, may contribute to AD risk in this population.",

keywords = "African Americans, Alzheimer's disease, Early onset, Genetics, Presenilins, Whole exome sequencing",

author = "Aurelie N'Songo and Carrasquillo, {Minerva M.} and Xue Wang and Thuy Nguyen and Yan Asmann and Younkin, {Steven G.} and Mariet Allen and Ranjan Duara and Custo, {Maria T.Greig} and Neill Graff-Radford and Nil{\"u}fer Ertekin-Taner",

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AU - N'Songo, Aurelie

AU - Carrasquillo, Minerva M.

AU - Wang, Xue

AU - Nguyen, Thuy

AU - Asmann, Yan

AU - Younkin, Steven G.

AU - Allen, Mariet

AU - Duara, Ranjan

AU - Custo, Maria T.Greig

AU - Graff-Radford, Neill

AU - Ertekin-Taner, Nilüfer

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AB - We conducted a comprehensive screening of rare coding variants in an African American cohort to identify novel pathogenic mutations within the early-onset Alzheimer's disease (EOAD) genes (APP, PSEN1, and PSEN2) in this understudied population. Whole-exome sequencing of 238 African American subjects identified 6 rare missense variants within the EOAD genes, which were observed in AD cases but never among controls. These variants were analyzed in an independent cohort of 300 African American subjects in which PSEN2:NM-000447:exon5:c.T331C:p.Phe111Leu and PSEN1-minilin rs777923890 variants were again not observed, indicating that these novel rare variants, may contribute to AD risk in this population.

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KW - Alzheimer's disease

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KW - Genetics

KW - Presenilins

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Comprehensive Screening for Disease Risk Variants in Early-Onset Alzheimer's Disease Genes in African Americans Identifies Novel PSEN Variants

Abstract

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