Details

Autor(en) / Beteiligte

• Nuytemans, Karen
• Rajabli, Farid
• Jean-Francois, Melissa
• Kurup, Jiji Thulaseedhara
• Adams, Larry D
• Starks, Takiyah D
• Whitehead, Patrice L
• Kunkle, Brian W
• Caban-Holt, Allison
• Haines, Jonathan L
• Cuccaro, Michael L
• Vance, Jeffery M
• Byrd, Goldie S
• Beecham, Gary W
• Reitz, Christiane
• Pericak-Vance, Margaret A

Titel

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

Ist Teil von

• Neurobiology of aging, 2024-01, Vol.133, p.125-133

Ort / Verlag

United States

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.