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.
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Aurelie
authors.initials: A
authors.lastname: N'Songo
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Minerva M
authors.initials: MM
authors.lastname: Carrasquillo
authors.affiliation: Department of Health Science Research, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Thuy
authors.initials: T
authors.lastname: Nguyen
authors.affiliation: Department of Health Science Research, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Asmann
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Younkin
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Mariet
authors.initials: M
authors.lastname: Allen
authors.affiliation: Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, FL, USA.
authors.forename: Ranjan
authors.initials: R
authors.lastname: Duara
authors.affiliation: Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, FL, USA.
authors.forename: Maria T Greig
authors.initials: MT
authors.lastname: Custo
authors.affiliation: Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Neill
authors.initials: N
authors.lastname: Graff-Radford
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.|Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Nilüfer
authors.initials: N
authors.lastname: Ertekin-Taner
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000208:ethnology* / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D053327:Apolipoprotein E4 / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D053764:Presenilin-1 / Q000235:genetics*; D053766:Presenilin-2 / Q000235:genetics*; D000073359:Exome Sequencing
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D053327:Apolipoprotein E4; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2
keywords: African Americans; Alzheimer’s disease; early onset; genetics; presenilins; whole exome sequencing