Genetic analyses in multiplex families confirms chromosome 5q35 as a risk locus for Alzheimer's Disease in individuals of African Ancestry.

Autor: Nuytemans K; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Dr. John T. MacDonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA., Rajabli F; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Dr. John T. MacDonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA., Jean-Francois M; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA., Kurup JT; Gertrude H. Sergievsky Center, Taub Institute for Research on the Aging Brain, Departments of Neurology, Psychiatry, and Epidemiology, College of Physicians and Surgeons, Columbia University, New York, NY, USA., Adams LD; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA., Starks TD; Maya Angelou Center for Health Equity, Wake Forest University, Winston-Salem, NC, USA., Whitehead PL; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA., Kunkle BW; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Dr. John T. MacDonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA., Caban-Holt A; Maya Angelou Center for Health Equity, Wake Forest University, Winston-Salem, NC, USA., Haines JL; Cleveland Institute for Computational Biology, Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA., Cuccaro ML; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Dr. John T. MacDonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA., Vance JM; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Dr. John T. MacDonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA., Byrd GS; Maya Angelou Center for Health Equity, Wake Forest University, Winston-Salem, NC, USA., Beecham GW; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Dr. John T. MacDonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA., Reitz C; Gertrude H. Sergievsky Center, Taub Institute for Research on the Aging Brain, Departments of Neurology, Psychiatry, and Epidemiology, College of Physicians and Surgeons, Columbia University, New York, NY, USA., Pericak-Vance MA; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Dr. John T. MacDonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA. Electronic address: mpericak@med.miami.edu.
Jazyk: angličtina
Zdroj: Neurobiology of aging [Neurobiol Aging] 2024 Jan; Vol. 133, pp. 125-133. Date of Electronic Publication: 2023 Oct 31.
DOI: 10.1016/j.neurobiolaging.2023.10.010
Abstrakt: There is a paucity of genetic studies of Alzheimer Disease (AD) in individuals of African Ancestry, despite evidence suggesting increased risk of AD in the African American (AA) population. We performed whole-genome sequencing (WGS) and multipoint linkage analyses in 51 multi-generational AA AD families ascertained through the Research in African American Alzheimer Disease Initiative (REAAADI) and the National Institute on Aging Late Onset Alzheimer's disease (NIA-LOAD) Family Based Study. Variants were prioritized on minor allele frequency (<0.01), functional potential of coding and noncoding variants, co-segregation with AD and presence in multi-ancestry ADSP release 3 WGS data. We identified a significant linkage signal on chromosome 5q35 (HLOD=3.3) driven by nine families. Haplotype segregation analysis in the family with highest LOD score identified a 3'UTR variant in INSYN2B with the most functional evidence. Four other linked AA families harbor within-family shared variants located in INSYN2B's promoter or enhancer regions. This AA family-based finding shows the importance of diversifying population-level genetic data to better understand the genetic determinants of AD on a global scale.
Competing Interests: Declaration of Competing Interest No conflicts of interest exist.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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