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 R Graff Radford, Nilufer Taner

Research output: Contribution to journalArticle

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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 languageEnglish (US)
Pages (from-to)1215-1222
Number of pages8
JournalJournal of Alzheimer's Disease
Volume56
Issue number4
DOIs
StatePublished - 2017

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Keywords

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

ASJC Scopus subject areas

  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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