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

Article type: Short Communication

Authors: N’Songo, Aurelie^a | Carrasquillo, Minerva M.^a | Wang, Xue^b | Nguyen, Thuy^a | Asmann, Yan^b | Younkin, Steven G.^a | Allen, Mariet^a | Duara, Ranjan^c | Custo, Maria T. Greig^c | Graff-Radford, Neill^d | Ertekin-Taner, Nilüfer^{a; d; *}

Affiliations: [a] Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA | [b] Department of Health Science Research, Mayo Clinic, Jacksonville, FL, USA | [c] Wien Center for Alzheimer’s Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, FL, USA | [d] Department of Neurology, Mayo Clinic, Jacksonville, FL, USA

Correspondence: [*] Correspondence to: Nilüfer Ertekin-Taner, Departments of Neuroscience and Neurology, Mayo Clinic, 4500 San Pablo Road, Birdsall 3, Jacksonville, FL 32224, USA. Tel.: +1 904 953 7103; E-mail: [email protected].

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

DOI: 10.3233/JAD-161185

Journal: Journal of Alzheimer's Disease, vol. 56, no. 4, pp. 1215-1222, 2017